Macrophages inhibit Coxiella burnetii by the ACOD1-itaconate pathway for containment of Q fever

Infection with the intracellular bacterium Coxiella (C.) burnetii can cause chronic Q fever with severe complications and limited treatment options. Here, we identify the enzyme cis-aconitate decarboxylase 1 (ACOD1 or IRG1) and its product itaconate as protective host immune pathway in Q fever. Infe...

Full description

Saved in:
Bibliographic Details
Published inbioRxiv
Main Authors Kohl, Lisa, Alam Siddique, Nur A, Bodendorfer, Barbara, Berger, Raffaela, Preikschat, Annica, Daniel, Christoph, Oelke, Martha, Mauermeir, Michael, Kai-Ting, Yang, Hayek, Inaya, Szperlinski, Mauela, Schulze-Luehrmann, Jan, Schleicher, Ulrike, Bozec, Aline, Kroenke, Gerhard, Murray, Peter J, Yamamoto, Masahiro, Schatz, Valentin, Jantsch, Joonathan, Oefner, Peter, Degrandi, Daniel, Pfeffer, Klaus, Rauber, Simon, Bogdan, Christian, Dettmer, Katja, Luhrmann, Anja, Lang, Roland
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 11.05.2022
Cold Spring Harbor Laboratory
Edition1.1
Subjects
Aconitate decarboxylase
Chronic infection
Gene expression
Germfree
Immunology
Infections
Inflammation
Macrophages
Pathogens
Q fever
Replication
Trachea
itaconate
Q fever
immunometabolism
Immune responsive gene 1 (Irg1)
Cis-aconitate decarboxylase 1 (Acod1)
Online AccessGet full text
ISSN2692-8205
2692-8205
DOI10.1101/2022.05.10.491306

Cover

Abstract Infection with the intracellular bacterium Coxiella (C.) burnetii can cause chronic Q fever with severe complications and limited treatment options. Here, we identify the enzyme cis-aconitate decarboxylase 1 (ACOD1 or IRG1) and its product itaconate as protective host immune pathway in Q fever. Infection of mice with C. burnetii induced expression of several anti-microbial candidate genes, including Acod1. In macrophages, Acod1 was essential for restricting C. burnetii replication, while other antimicrobial pathways were dispensable. Intratracheal or intraperitoneal infection of Acod1-/- mice caused increased C. burnetii burden, significant weight loss and stronger inflammatory gene expression. Exogenously added itaconate restored pathogen control in Acod1-/- mouse macrophages and blocked replication in human macrophages. In axenic cultures, itaconate directly inhibited growth of C. burnetii. Finally, treatment of infected Acod1-/- mice with itaconate efficiently reduced the tissue pathogen load. Thus, ACOD1-derived itaconate is a key factor in the macrophage-mediated defense against C. burnetii and may be exploited for novel therapeutic approaches in chronic Q fever. Competing Interest Statement The authors have declared no competing interest.
AbstractList Infection with the intracellular bacterium Coxiella (C.) burnetii can cause chronic Q fever with severe complications and limited treatment options. Here, we identify the enzyme cis-aconitate decarboxylase 1 (ACOD1 or IRG1) and its product itaconate as protective host immune pathway in Q fever. Infection of mice with C. burnetii induced expression of several anti-microbial candidate genes, including Acod1. In macrophages, Acod1 was essential for restricting C. burnetii replication, while other antimicrobial pathways were dispensable. Intratracheal or intraperitoneal infection of Acod1-/- mice caused increased C. burnetii burden, significant weight loss and stronger inflammatory gene expression. Exogenously added itaconate restored pathogen control in Acod1-/- mouse macrophages and blocked replication in human macrophages. In axenic cultures, itaconate directly inhibited growth of C. burnetii. Finally, treatment of infected Acod1-/- mice with itaconate efficiently reduced the tissue pathogen load. Thus, ACOD1-derived itaconate is a key factor in the macrophage-mediated defense against C. burnetii and may be exploited for novel therapeutic approaches in chronic Q fever. Competing Interest Statement The authors have declared no competing interest.
Infection with the intracellular bacterium Coxiella (C.) burnetii can cause chronic Q fever with severe complications and limited treatment options. Here, we identify the enzyme cis- aconitate decarboxylase 1 (ACOD1 or IRG1) and its product itaconate as protective host immune pathway in Q fever. Infection of mice with C. burnetii induced expression of several anti-microbial candidate genes, including Acod1. In macrophages, Acod1 was essential for restricting C. burnetii replication, while other antimicrobial pathways were dispensable. Intratracheal or intraperitoneal infection of Acod1-/- mice caused increased C. burnetii burden, significant weight loss and stronger inflammatory gene expression. Exogenously added itaconate restored pathogen control in Acod1-/- mouse macrophages and blocked replication in human macrophages. In axenic cultures, itaconate directly inhibited growth of C. burnetii. Finally, treatment of infected Acod1-/-mice with itaconate efficiently reduced the tissue pathogen load. Thus, ACOD1-derived itaconate is a key factor in the macrophage-mediated defense against C. burnetii and may be exploited for novel therapeutic approaches in chronic Q fever.
Author Alam Siddique, Nur A
Kai-Ting, Yang
Schulze-Luehrmann, Jan
Bogdan, Christian
Kroenke, Gerhard
Dettmer, Katja
Preikschat, Annica
Oefner, Peter
Murray, Peter J
Jantsch, Joonathan
Berger, Raffaela
Rauber, Simon
Mauermeir, Michael
Kohl, Lisa
Bozec, Aline
Luhrmann, Anja
Szperlinski, Mauela
Oelke, Martha
Pfeffer, Klaus
Schleicher, Ulrike
Yamamoto, Masahiro
Schatz, Valentin
Daniel, Christoph
Bodendorfer, Barbara
Lang, Roland
Degrandi, Daniel
Hayek, Inaya
Author_xml – sequence: 1
  givenname: Lisa
  surname: Kohl
  fullname: Kohl, Lisa
– sequence: 2
  givenname: Nur
  surname: Alam Siddique
  middlename: A
  fullname: Alam Siddique, Nur A
– sequence: 3
  givenname: Barbara
  surname: Bodendorfer
  fullname: Bodendorfer, Barbara
– sequence: 4
  givenname: Raffaela
  surname: Berger
  fullname: Berger, Raffaela
– sequence: 5
  givenname: Annica
  surname: Preikschat
  fullname: Preikschat, Annica
– sequence: 6
  givenname: Christoph
  surname: Daniel
  fullname: Daniel, Christoph
– sequence: 7
  givenname: Martha
  surname: Oelke
  fullname: Oelke, Martha
– sequence: 8
  givenname: Michael
  surname: Mauermeir
  fullname: Mauermeir, Michael
– sequence: 9
  givenname: Yang
  surname: Kai-Ting
  fullname: Kai-Ting, Yang
– sequence: 10
  givenname: Inaya
  surname: Hayek
  fullname: Hayek, Inaya
– sequence: 11
  givenname: Mauela
  surname: Szperlinski
  fullname: Szperlinski, Mauela
– sequence: 12
  givenname: Jan
  surname: Schulze-Luehrmann
  fullname: Schulze-Luehrmann, Jan
– sequence: 13
  givenname: Ulrike
  surname: Schleicher
  fullname: Schleicher, Ulrike
– sequence: 14
  givenname: Aline
  surname: Bozec
  fullname: Bozec, Aline
– sequence: 15
  givenname: Gerhard
  surname: Kroenke
  fullname: Kroenke, Gerhard
– sequence: 16
  givenname: Peter
  surname: Murray
  middlename: J
  fullname: Murray, Peter J
– sequence: 17
  givenname: Masahiro
  surname: Yamamoto
  fullname: Yamamoto, Masahiro
– sequence: 18
  givenname: Valentin
  surname: Schatz
  fullname: Schatz, Valentin
– sequence: 19
  givenname: Joonathan
  surname: Jantsch
  fullname: Jantsch, Joonathan
– sequence: 20
  givenname: Peter
  surname: Oefner
  fullname: Oefner, Peter
– sequence: 21
  givenname: Daniel
  surname: Degrandi
  fullname: Degrandi, Daniel
– sequence: 22
  givenname: Klaus
  surname: Pfeffer
  fullname: Pfeffer, Klaus
– sequence: 23
  givenname: Simon
  surname: Rauber
  fullname: Rauber, Simon
– sequence: 24
  givenname: Christian
  surname: Bogdan
  fullname: Bogdan, Christian
– sequence: 25
  givenname: Katja
  surname: Dettmer
  fullname: Dettmer, Katja
– sequence: 26
  givenname: Anja
  surname: Luhrmann
  fullname: Luhrmann, Anja
– sequence: 27
  givenname: Roland
  surname: Lang
  fullname: Lang, Roland
BookMark eNpNUMtOwzAQtFCRKKUfwM0SFy4paztx4mMVnlJRhdS7tW4d4qqNg-OW5u8JKgdOOzsajWbmmowa31hCbhnMGAP2wIHzGWSz4U8VEyAvyJhLxZOCQzb6h6_ItOu2AMCVZCJPx0S_4zr4tsZP21HX1M64SEt_cna3Q2oOobHROWp6GmtL5-XykSUu4to3GC1tMdbf2NPKBzpQEV2zt02kvqIftLJHG27IZYW7zk7_7oSsnp9W5WuyWL68lfNFYhikMmGKZTAEV4XFwnBpMmaqXJk0F4UoeJ7JDW5yuYaiEgYUCCwUUyKzgGgGbkLuz7bG-XByR90Gt8fQ699pNGSagT5PM0jvztI2-K-D7aLe-qHmEE5zKTmTOQgpfgClcmOZ
Cites_doi 10.1099/mic.0.001050
10.1093/braincomms/fcab187
10.7554/eLife.11479
10.3389/fimmu.2019.00165
10.1007/s10753-020-01352-4
10.1128/IAI.00172-20
10.1111/cmi.12634
10.1126/sciimmunol.abc1884
10.1128/IAI.00744-19
ContentType Paper
Copyright 2022. Notwithstanding the ProQuest Terms and conditions, you may use this content in accordance with the associated terms available at https://www.biorxiv.org/content/10.1101/2022.05.10.491306v1
2022, Posted by Cold Spring Harbor Laboratory
Copyright_xml – notice: 2022. Notwithstanding the ProQuest Terms and conditions, you may use this content in accordance with the associated terms available at https://www.biorxiv.org/content/10.1101/2022.05.10.491306v1
– notice: 2022, Posted by Cold Spring Harbor Laboratory
DBID 8FE
8FH
ABUWG
AFKRA
AZQEC
BBNVY
BENPR
BHPHI
CCPQU
DWQXO
GNUQQ
HCIFZ
LK8
M7P
PHGZM
PHGZT
PIMPY
PKEHL
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
FX.
DOI 10.1101/2022.05.10.491306
DatabaseName ProQuest SciTech Collection
ProQuest Natural Science Collection
ProQuest Central (Alumni)
ProQuest Central UK/Ireland
ProQuest Central Essentials
Biological Science Collection
ProQuest Central
Natural Science Collection
ProQuest One Community College
ProQuest Central
ProQuest Central Student
SciTech Premium Collection
Biological Sciences
Biological science database
ProQuest Central Premium
ProQuest One Academic (New)
Publicly Available Content Database
ProQuest One Academic Middle East (New)
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
bioRxiv
DatabaseTitle Publicly Available Content Database
ProQuest Central Student
ProQuest One Academic Middle East (New)
ProQuest Biological Science Collection
ProQuest Central Essentials
ProQuest One Academic Eastern Edition
ProQuest Central (Alumni Edition)
SciTech Premium Collection
ProQuest One Community College
ProQuest Natural Science Collection
Biological Science Database
ProQuest SciTech Collection
ProQuest Central China
ProQuest Central
ProQuest One Applied & Life Sciences
ProQuest One Academic UKI Edition
Natural Science Collection
ProQuest Central Korea
Biological Science Collection
ProQuest Central (New)
ProQuest One Academic
ProQuest One Academic (New)
DatabaseTitleList Publicly Available Content Database
Database_xml – sequence: 1
  dbid: FX.
  name: bioRxiv
  url: https://www.biorxiv.org/
  sourceTypes: Open Access Repository
– sequence: 2
  dbid: BENPR
  name: AUTh Library subscriptions: ProQuest Central
  url: http://www.proquest.com/pqcentral?accountid=15518
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
EISSN 2692-8205
Edition 1.1
ExternalDocumentID 2022.05.10.491306v1
Genre Working Paper/Pre-Print
GroupedDBID 8FE
8FH
ABUWG
AFKRA
ALMA_UNASSIGNED_HOLDINGS
AZQEC
BBNVY
BENPR
BHPHI
CCPQU
DWQXO
GNUQQ
HCIFZ
LK8
M7P
NQS
PHGZM
PHGZT
PIMPY
PKEHL
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
PROAC
RHI
FX.
ID FETCH-LOGICAL-b1046-1915030698ea8b26b51bf79b4738382756dad76c08f3b0903a891935e0aab8f3
IEDL.DBID BENPR
ISSN 2692-8205
IngestDate Tue Jan 07 18:57:59 EST 2025
Fri Jul 25 09:18:09 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed false
IsScholarly false
Keywords itaconate
Q fever
immunometabolism
Immune responsive gene 1 (Irg1)
Cis-aconitate decarboxylase 1 (Acod1)
Language English
License The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-b1046-1915030698ea8b26b51bf79b4738382756dad76c08f3b0903a891935e0aab8f3
Notes SourceType-Working Papers-1
ObjectType-Working Paper/Pre-Print-1
content type line 50
Competing Interest Statement: The authors have declared no competing interest.
ORCID 0000-0001-6281-0357
0000-0001-6329-9802
OpenAccessLink https://www.proquest.com/docview/2662167036?pq-origsite=%requestingapplication%&accountid=15518
PQID 2662167036
PQPubID 2050091
PageCount 51
ParticipantIDs biorxiv_primary_2022_05_10_491306
proquest_journals_2662167036
PublicationCentury 2000
PublicationDate 20220511
PublicationDateYYYYMMDD 2022-05-11
PublicationDate_xml – month: 05
  year: 2022
  text: 20220511
  day: 11
PublicationDecade 2020
PublicationPlace Cold Spring Harbor
PublicationPlace_xml – name: Cold Spring Harbor
PublicationTitle bioRxiv
PublicationYear 2022
Publisher Cold Spring Harbor Laboratory Press
Cold Spring Harbor Laboratory
Publisher_xml – name: Cold Spring Harbor Laboratory Press
– name: Cold Spring Harbor Laboratory
References Seshadri, Paulsen, Eisen, Read, Nelson, Nelson, Ward, Tettelin, Davidsen, Beanan, Deboy, Daugherty, Brinkac, Madupu, Dodson, Khouri, Lee, Carty, Scanlan, Heinzen, Thompson, Samuel, Fraser, Heidelberg (2022.05.10.491306v1.46) 2003; 100
Lührmann, Newton, Bonazzi (2022.05.10.491306v1.28) 2017; 413
Bogdan (2022.05.10.491306v1.5) 2015; 36
Howe, Barrows, Lindstrom, Heinzen (2022.05.10.491306v1.19) 2002; 70
Ruetz, Campanello, Purchal, Shen, McDevitt, Gouda, Wakabayashi, Zhu, Rubin, Warncke, Mootha, Koutmos, Banerjee (2022.05.10.491306v1.42) 2019; 366
Degrandi, Hoffmann, Beuter-Gunia, Pfeffer (2022.05.10.491306v1.10) 2009; 29
Michelucci, Cordes, Ghelfi, Pailot, Reiling, Goldmann, Binz, Wegner, Tallam, Rausell, Buttini, Linster, Medina, Balling, Hiller (2022.05.10.491306v1.30) 2013; 110
O’Neill, Pearce (2022.05.10.491306v1.36) 2016; 213
Lacey, Ponzilacqua-Silva, Chambers, Dadelahi, Skyberg (2022.05.10.491306v1.27) 2021; 89
Chen, Sun, Boot, Shao, Chang, Wang, Lam, Lara-Tejero, Rego, Galan (2022.05.10.491306v1.7) 2020; 369
Demars, Vitali, Comein, Carlier, Azouz, Goriely, Smout, Flamand, Van Gysel, Wouters, Abendroth, Edwards, Machelart, Hoffmann, Brodin, De Bolle, Muraille (2022.05.10.491306v1.12) 2021; 17
Swain, Bambouskova, Kim, Andhey, Duncan, Auclair, Chubukov, Simons, Roddy, Stewart, Artyomov (2022.05.10.491306v1.49) 2020; 2
Omsland, Cockrell, Howe, Fischer, Virtaneva, Sturdevant, Porcella, Heinzen (2022.05.10.491306v1.38) 2009; 106
Matthiesen, Zaeck, Franzke, Jahnke, Fricke, Mauermeir, Finke, Lührmann, Knittler (2022.05.10.491306v1.29) 2020; 88
Gidon, Louet, Rost, Bruheim, Flo (2022.05.10.491306v1.16) 2021; 12
Zamboni, Rabinovitch (2022.05.10.491306v1.56) 2003; 71
Naujoks, Tabeling, Dill, Hoffmann, Brown, Kunze, Kempa, Peter, Mollenkopf, Dorhoi, Kershaw, Gruber, Sander, Witzenrath, Herold, Nerlich, Hocke, van Driel, Suttorp, Bedoui, Hilbi, Trost, Opitz (2022.05.10.491306v1.35) 2016; 12
Zamboni, Campos, Torrecilhas, Kiss, Samuel, Golenbock, Lauw, Roy, Almeida, Gazzinelli (2022.05.10.491306v1.55) 2004; 279
Hall, Boyle, Astin, Flores, Oehlers, Sanderson, Ellett, Lieschke, Crosier, Crosier (2022.05.10.491306v1.17) 2013; 18
Ramstead, Robison, Blackwell, Jerome, Freedman, Lubick, Hedges, Jutila (2022.05.10.491306v1.40) 2016; 84
Anderson, Bijlmer, Fournier, Graves, Hartzell, Kersh, Limonard, Marrie, Massung, McQuiston, Nicholson, Paddock, Sexton (2022.05.10.491306v1.2) 2013; 62
Ogger, Albers, Hewitt, O’Sullivan, Powell, Calamita, Ghai, Walker, McErlean, Saunders, Kingston, Molyneaux, Halket, Gray, Chambers, Maher, Lloyd, Byrne (2022.05.10.491306v1.37) 2020; 5
Zhang, Jiao, Li, Liang, Jia, Nie, Zhang (2022.05.10.491306v1.57) 2021; 44
Kohl, Hayek, Daniel, Schulze-Luhrmann, Bodendorfer, Lührmann, Lang (2022.05.10.491306v1.23) 2019; 10
van Roeden, Wever, Kampschreur, Gruteke, van der Hoek, Hoepelman, Bleeker-Rovers, Oosterheert (2022.05.10.491306v1.51) 2019; 25
Ryan, O’Neill (2022.05.10.491306v1.43) 2020; 38
Wu, Chen, Wang, Tang, Kang (2022.05.10.491306v1.53) 2020; 17
Kim, Shenoy, Kumar, Das, Tiwari, MacMicking (2022.05.10.491306v1.22) 2011; 332
Mills, Ryan, Prag, Dikovskaya, Menon, Zaslona, Jedrychowski, Costa, Higgins, Hams, Szpyt, Runtsch, King, McGouran, Fischer, Kessler, McGettrick, Hughes, Carroll, Booty, Knatko, Meakin, Ashford, Modis, Brunori, Sevin, Fallon, Caldwell, Kunji, Chouchani, Frezza, Dinkova-Kostova, Hartley, Murphy, O’Neill (2022.05.10.491306v1.31) 2018; 556
Nair, Huynh, Lampropoulou, Loginicheva, Esaulova, Gounder, Boon, Schwarzkopf, Bradstreet, Edelson, Artyomov, Stallings, Diamond (2022.05.10.491306v1.34) 2018; 215
Duncan, Lupien, Behr, Auclair (2022.05.10.491306v1.13) 2021; 167
Berger, Wachsmuth, Waldhier, Renner-Sattler, Thomas, Chaturvedi, Niller, Bumes, Hau, Proescholdt, Gronwald, Heuser, Kreutz, Oefner, Dettmer (2022.05.10.491306v1.4) 2021; 13
Shi, Blumenthal, Hickey, Gandotra, Levy, Ehrt (2022.05.10.491306v1.47) 2005; 175
Kuo, Weng, Scofield, Furnas, Paraiso, Yu, Yen (2022.05.10.491306v1.26) 2021; 3
Schafer, Eckart, Schmid, Cagkoylu, Hof, Muller, Amin, Lührmann (2022.05.10.491306v1.45) 2017; 19
Degrandi, Kravets, Konermann, Beuter-Gunia, Klumpers, Lahme, Wischmann, Mausberg, Beer-Hammer, Pfeffer (2022.05.10.491306v1.11) 2013; 110
Eldin, Melenotte, Mediannikov, Ghigo, Million, Edouard, Mege, Maurin, Raoult (2022.05.10.491306v1.14) 2017; 30
Ammerdorffer, Schoffelen, Gresnigt, Oosting, den Brok, Abdollahi- Roodsaz, Kanneganti, de Jong, van Deuren, Roest, Rebel, Netea, Joosten, Sprong (2022.05.10.491306v1.1) 2015; 211
Korner, Cook, Riminton, Lemckert, Hoek, Ledermann, Kontgen, Fazekas de St Groth, Sedgwick (2022.05.10.491306v1.24) 1997; 27
Peng, Monack (2022.05.10.491306v1.39) 2010; 78
Singh, Singh, Jha, Naik, Joseph, Giri, Kumar (2022.05.10.491306v1.48) 2021; 2
Ganesan, Roy (2022.05.10.491306v1.15) 2019; 15
Kravets, Degrandi, Ma, Peulen, Klumpers, Felekyan, Kuhnemuth, Weidtkamp-Peters, Seidel, Pfeffer (2022.05.10.491306v1.25) 2016; 5
Jessop, Buntyn, Schwarz, Wehrly, Scott, Bosio (2022.05.10.491306v1.20) 2020; 88
Van de Velde, Gingras, Pelletier, Murray (2022.05.10.491306v1.50) 2016; 23
Muller, Steinhoff, Reis, Hemmi, Pavlovic, Zinkernagel, Aguet (2022.05.10.491306v1.32) 1994; 264
Williams, O’Neill (2022.05.10.491306v1.52) 2018; 9
Andoh, Zhang, Russell-Lodrigue, Shive, Weeks, Samuel (2022.05.10.491306v1.3) 2007; 75
Raoult, Drancourt, Vestris (2022.05.10.491306v1.41) 1990; 34
Sandoz, Beare, Cockrell, Heinzen (2022.05.10.491306v1.44) 2016; 82
Carey, Newton, Luhrmann, Roy (2022.05.10.491306v1.6) 2011; 7
Hayek, Fischer, Schulze-Luehrmann, Dettmer, Sobotta, Schatz, Kohl, Boden, Lang, Oefner, Wirtz, Jantsch, Lührmann (2022.05.10.491306v1.18) 2019; 26
Kampschreur, Delsing, Groenwold, Wegdam-Blans, Bleeker- Rovers, de Jager-Leclercq, Hoepelman, van Kasteren, Buijs, Renders, Nabuurs-Franssen, Oosterheert, Wever (2022.05.10.491306v1.21) 2014; 52
Yamamoto, Okuyama, Ma, Kimura, Kamiyama, Saiga, Ohshima, Sasai, Kayama, Okamoto, Huang, Soldati-Favre, Horie, Takeda, Takeda (2022.05.10.491306v1.54) 2012; 37
Cordes, Lucas, Divakaruni, Murphy, Cabrales, Metallo (2022.05.10.491306v1.8) 2020; 32
Murphy, O’Neill (2022.05.10.491306v1.33) 2018; 174
Cordes, Wallace, Michelucci, Divakaruni, Sapcariu, Sousa, Koseki, Cabrales, Murphy, Hiller, Metallo (2022.05.10.491306v1.9) 2016; 291
References_xml – volume: 12
  start-page: e0212121
  year: 2021
  ident: 2022.05.10.491306v1.16
  article-title: The Tumor Necrosis Factor Alpha and Interleukin 6 Auto-paracrine Signaling Loop Controls Mycobacterium avium Infection via Induction of IRF1/IRG1 in Human Primary Macrophages
  publication-title: mBio
– volume: 369
  start-page: 450
  year: 2020
  end-page: 455
  ident: 2022.05.10.491306v1.7
  article-title: Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella
  publication-title: Science
– volume: 84
  start-page: 940
  year: 2016
  end-page: 949
  ident: 2022.05.10.491306v1.40
  article-title: Roles of Toll-Like Receptor 2 (TLR2), TLR4, and MyD88 during Pulmonary Coxiella burnetii Infection
  publication-title: Infect Immun
– volume: 15
  start-page: e1007955
  year: 2019
  ident: 2022.05.10.491306v1.15
  article-title: Host cell depletion of tryptophan by IFNgamma-induced Indoleamine 2,3-dioxygenase 1 (IDO1) inhibits lysosomal replication of Coxiella burnetii
  publication-title: PLoS Pathog
– volume: 264
  start-page: 1918
  year: 1994
  end-page: 1921
  ident: 2022.05.10.491306v1.32
  article-title: Functional role of type I and type II interferons in antiviral defense
  publication-title: Science
– volume: 366
  start-page: 589
  year: 2019
  end-page: 593
  ident: 2022.05.10.491306v1.42
  article-title: Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair
  publication-title: Science
– volume: 332
  start-page: 717
  year: 2011
  end-page: 721
  ident: 2022.05.10.491306v1.22
  article-title: A family of IFN-gamma-inducible 65-kD GTPases protects against bacterial infection
  publication-title: Science
– volume: 279
  start-page: 54405
  year: 2004
  end-page: 54415
  ident: 2022.05.10.491306v1.55
  article-title: Stimulation of toll-like receptor 2 by Coxiella burnetii is required for macrophage production of pro-inflammatory cytokines and resistance to infection
  publication-title: J Biol Chem
– volume: 167
  year: 2021
  ident: 2022.05.10.491306v1.13
  article-title: Effect of pH on the antimicrobial activity of the macrophage metabolite itaconate
  publication-title: Microbiology (Reading)
  doi: 10.1099/mic.0.001050
– volume: 3
  start-page: fcab187
  year: 2021
  ident: 2022.05.10.491306v1.26
  article-title: Immunoresponsive gene 1 modulates the severity of brain injury in cerebral ischaemia
  publication-title: Brain Commun
  doi: 10.1093/braincomms/fcab187
– volume: 5
  year: 2016
  ident: 2022.05.10.491306v1.25
  article-title: Guanylate binding proteins directly attack Toxoplasma gondii via supramolecular complexes
  publication-title: eLife
  doi: 10.7554/eLife.11479
– volume: 38
  start-page: 289
  year: 2020
  end-page: 313
  ident: 2022.05.10.491306v1.43
  article-title: Krebs Cycle Reborn in Macrophage Immunometabolism
  publication-title: Annu Rev Immunol
– volume: 175
  start-page: 3318
  year: 2005
  end-page: 3328
  ident: 2022.05.10.491306v1.47
  article-title: Expression of Many Immunologically Important Genes in Mycobacterium tuberculosis-Infected Macrophages Is Independent of Both TLR2 and TLR4 but Dependent on IFN-{alpha}{beta} Receptor and STAT1
  publication-title: J Immunol
– volume: 211
  start-page: 978
  year: 2015
  end-page: 987
  ident: 2022.05.10.491306v1.1
  article-title: Recognition of Coxiella burnetii by toll-like receptors and nucleotide-binding oligomerization domain-like receptors
  publication-title: J Infect Dis
– volume: 71
  start-page: 1225
  year: 2003
  end-page: 1233
  ident: 2022.05.10.491306v1.56
  article-title: Nitric oxide partially controls Coxiella burnetii phase II infection in mouse primary macrophages
  publication-title: Infect Immun
– volume: 75
  start-page: 3245
  year: 2007
  end-page: 3255
  ident: 2022.05.10.491306v1.3
  article-title: T cells are essential for bacterial clearance, and gamma interferon, tumor necrosis factor alpha, and B cells are crucial for disease development in Coxiella burnetii infection in mice
  publication-title: Infect Immun
– volume: 413
  start-page: 243
  year: 2017
  end-page: 268
  ident: 2022.05.10.491306v1.28
  article-title: Beginning to Understand the Role of the Type IV Secretion System Effector Proteins in Coxiella burnetii Pathogenesis
  publication-title: Curr Top Microbiol Immunol
– volume: 10
  start-page: 165
  year: 2019
  ident: 2022.05.10.491306v1.23
  article-title: MyD88 Is Required for Efficient Control of Coxiella burnetii Infection and Dissemination
  publication-title: Front Immunol
  doi: 10.3389/fimmu.2019.00165
– volume: 29
  start-page: 55
  year: 2009
  end-page: 67
  ident: 2022.05.10.491306v1.10
  article-title: The proinflammatory cytokine-induced IRG1 protein associates with mitochondria
  publication-title: J Interferon Cytokine Res
– volume: 556
  start-page: 113
  year: 2018
  end-page: 117
  ident: 2022.05.10.491306v1.31
  article-title: Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1
  publication-title: Nature
– volume: 36
  start-page: 161
  year: 2015
  end-page: 178
  ident: 2022.05.10.491306v1.5
  article-title: Nitric oxide synthase in innate and adaptive immunity: an update
  publication-title: Trends Immunol
– volume: 78
  start-page: 2723
  year: 2010
  end-page: 2733
  ident: 2022.05.10.491306v1.39
  article-title: Indoleamine 2,3-dioxygenase 1 is a lung-specific innate immune defense mechanism that inhibits growth of Francisella tularensis tryptophan auxotrophs
  publication-title: Infect Immun
– volume: 26
  start-page: 3502
  year: 2019
  end-page: 3510 e3506
  ident: 2022.05.10.491306v1.18
  article-title: Limitation of TCA Cycle Intermediates Represents an Oxygen-Independent Nutritional Antibacterial Effector Mechanism of Macrophages
  publication-title: Cell Reports
– volume: 32
  start-page: 122
  year: 2020
  end-page: 135
  ident: 2022.05.10.491306v1.8
  article-title: Itaconate modulates tricarboxylic acid and redox metabolism to mitigate reperfusion injury
  publication-title: Mol Metab
– volume: 34
  start-page: 1512
  year: 1990
  end-page: 1514
  ident: 2022.05.10.491306v1.41
  article-title: Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells
  publication-title: Antimicrob Agents Chemother
– volume: 2
  start-page: 100277
  year: 2021
  ident: 2022.05.10.491306v1.48
  article-title: Integrative metabolomics and transcriptomics identifies itaconate as an adjunct therapy to treat ocular bacterial infection
  publication-title: Cell Rep Med
– volume: 13
  start-page: 1756
  year: 2021
  ident: 2022.05.10.491306v1.4
  article-title: Lactonization of the Oncometabolite D-2-Hydroxyglutarate Produces a Novel Endogenous Metabolite
  publication-title: Cancers (Basel)
– volume: 106
  start-page: 4430
  year: 2009
  end-page: 4434
  ident: 2022.05.10.491306v1.38
  article-title: Host cell-free growth of the Q fever bacterium Coxiella burnetii
  publication-title: Proc Natl Acad Sci U S A
– volume: 27
  start-page: 2600
  year: 1997
  end-page: 2609
  ident: 2022.05.10.491306v1.24
  article-title: Distinct roles for lymphotoxin-alpha and tumor necrosis factor in organogenesis and spatial organization of lymphoid tissue
  publication-title: Eur J Immunol
– volume: 70
  start-page: 5140
  year: 2002
  end-page: 5147
  ident: 2022.05.10.491306v1.19
  article-title: Nitric oxide inhibits Coxiella burnetii replication and parasitophorous vacuole maturation
  publication-title: Infect Immun
– volume: 7
  start-page: e1002056
  year: 2011
  ident: 2022.05.10.491306v1.6
  article-title: The Coxiella burnetii Dot/Icm system delivers a unique repertoire of type IV effectors into host cells and is required for intracellular replication
  publication-title: PLoS Pathog
– volume: 110
  start-page: 7820
  year: 2013
  end-page: 7825
  ident: 2022.05.10.491306v1.30
  article-title: Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production
  publication-title: Proc Natl Acad Sci U S A
– volume: 23
  start-page: 389
  year: 2016
  end-page: 390
  ident: 2022.05.10.491306v1.50
  article-title: Issues with the Specificity of Immunological Reagents for Murine IDO1
  publication-title: Cell Metab
– volume: 30
  start-page: 115
  year: 2017
  end-page: 190
  ident: 2022.05.10.491306v1.14
  article-title: From Q Fever to Coxiella burnetii Infection: a Paradigm Change
  publication-title: Clin Microbiol Rev
– volume: 82
  start-page: 3042
  year: 2016
  end-page: 3051
  ident: 2022.05.10.491306v1.44
  article-title: Complementation of Arginine Auxotrophy for Genetic Transformation of Coxiella burnetii by Use of a Defined Axenic Medium
  publication-title: Applied and environmental microbiology
– volume: 44
  start-page: 549
  year: 2021
  end-page: 557
  ident: 2022.05.10.491306v1.57
  article-title: Dimethyl Itaconate Alleviates the Inflammatory Responses of Macrophages in Sepsis
  publication-title: Inflammation
  doi: 10.1007/s10753-020-01352-4
– volume: 213
  start-page: 15
  year: 2016
  end-page: 23
  ident: 2022.05.10.491306v1.36
  article-title: Immunometabolism governs dendritic cell and macrophage function
  publication-title: J Exp Med
– volume: 18
  start-page: 265
  year: 2013
  end-page: 278
  ident: 2022.05.10.491306v1.17
  article-title: Immunoresponsive gene 1 augments bactericidal activity of macrophage-lineage cells by regulating beta-oxidation-dependent mitochondrial ROS production
  publication-title: Cell Metab
– volume: 88
  year: 2020
  ident: 2022.05.10.491306v1.29
  article-title: Coxiella burnetii-Infected NK Cells Release Infectious Bacteria by Degranulation
  publication-title: Infect Immun
  doi: 10.1128/IAI.00172-20
– volume: 291
  start-page: 14274
  year: 2016
  end-page: 14284
  ident: 2022.05.10.491306v1.9
  article-title: Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels
  publication-title: J Biol Chem
– volume: 19
  year: 2017
  ident: 2022.05.10.491306v1.45
  article-title: Nuclear trafficking of the anti-apoptotic Coxiella burnetii effector protein AnkG requires binding to p32 and Importin-alpha1
  publication-title: Cell Microbiol
  doi: 10.1111/cmi.12634
– volume: 17
  start-page: e1009887
  year: 2021
  ident: 2022.05.10.491306v1.12
  article-title: Aconitate decarboxylase 1 participates in the control of pulmonary Brucella infection in mice
  publication-title: PLoS Pathog
– volume: 17
  start-page: 822
  year: 2020
  end-page: 833
  ident: 2022.05.10.491306v1.53
  article-title: ACOD1 in immunometabolism and disease
  publication-title: Cell Mol Immunol
– volume: 37
  start-page: 302
  year: 2012
  end-page: 313
  ident: 2022.05.10.491306v1.54
  article-title: A cluster of interferon-gamma-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii
  publication-title: Immunity
– volume: 62
  start-page: 1
  year: 2013
  end-page: 30
  ident: 2022.05.10.491306v1.2
  article-title: Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group
  publication-title: MMWR Recomm Rep
– volume: 89
  start-page: e0015621
  year: 2021
  ident: 2022.05.10.491306v1.27
  article-title: MyD88-Dependent Glucose Restriction and Itaconate Production Control Brucella Infection
  publication-title: Infect Immun
– volume: 25
  start-page: 1390
  year: 2019
  end-page: 1398
  ident: 2022.05.10.491306v1.51
  article-title: Chronic Q fever-related complications and mortality: data from a nationwide cohort
  publication-title: Clin Microbiol Infect
– volume: 215
  start-page: 1035
  year: 2018
  end-page: 1045
  ident: 2022.05.10.491306v1.34
  article-title: Irg1 expression in myeloid cells prevents immunopathology during M. tuberculosis infection
  publication-title: J Exp Med
– volume: 52
  start-page: 1637
  year: 2014
  end-page: 1643
  ident: 2022.05.10.491306v1.21
  article-title: Chronic Q fever in the Netherlands 5 years after the start of the Q fever epidemic: results from the Dutch chronic Q fever database
  publication-title: J Clin Microbiol
– volume: 5
  year: 2020
  ident: 2022.05.10.491306v1.37
  article-title: Itaconate controls the severity of pulmonary fibrosis
  publication-title: Sci Immunol
  doi: 10.1126/sciimmunol.abc1884
– volume: 9
  start-page: 141
  year: 2018
  ident: 2022.05.10.491306v1.52
  article-title: A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation
  publication-title: FrontIimmunol
– volume: 100
  start-page: 5455
  year: 2003
  end-page: 5460
  ident: 2022.05.10.491306v1.46
  article-title: Complete genome sequence of the Q-fever pathogen Coxiella burnetii
  publication-title: Proc Natl Acad Sci U S A
– volume: 2
  start-page: 594
  year: 2020
  end-page: 602
  ident: 2022.05.10.491306v1.49
  article-title: Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages
  publication-title: Nat Metab
– volume: 12
  start-page: e1005408
  year: 2016
  ident: 2022.05.10.491306v1.35
  article-title: IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid
  publication-title: PLoS Pathog
– volume: 110
  start-page: 294
  year: 2013
  end-page: 299
  ident: 2022.05.10.491306v1.11
  article-title: Murine guanylate binding protein 2 (mGBP2) controls Toxoplasma gondii replication
  publication-title: Proc Natl Acad Sci U S A
– volume: 174
  start-page: 780
  year: 2018
  end-page: 784
  ident: 2022.05.10.491306v1.33
  article-title: Krebs Cycle Reimagined: The Emerging Roles of Succinate and Itaconate as Signal Transducers
  publication-title: Cell
– volume: 88
  year: 2020
  ident: 2022.05.10.491306v1.20
  article-title: Interferon Gamma Reprograms Host Mitochondrial Metabolism through Inhibition of Complex II To Control Intracellular Bacterial Replication
  publication-title: Infect Immun
  doi: 10.1128/IAI.00744-19
SSID ssj0002961374
Score 1.6582485
SecondaryResourceType preprint
Snippet Infection with the intracellular bacterium Coxiella (C.) burnetii can cause chronic Q fever with severe complications and limited treatment options. Here, we...
SourceID biorxiv
proquest
SourceType Open Access Repository
Aggregation Database
SubjectTerms Aconitate decarboxylase
Chronic infection
Gene expression
Germfree
Immunology
Infections
Inflammation
Macrophages
Pathogens
Q fever
Replication
Trachea
SummonAdditionalLinks – databaseName: bioRxiv
  dbid: FX.
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3NS8MwFA-6IXjzE6dTInitNF3StEeZjiH4BRN2K3ltwnJpx1Z1--99b60i6MFjA03p-_7i_Ri7EqGJrR6oQNAIjQTtApAyD0ShYqfBiqiZ8n2Mx6_yfqqmP6C-aKwSfLVY-fdNH58GttH6NsodCsrVI1q1ic8yRfsbb7Muipgi1IbR9Pq7vBKl6Ke0bPuYf76JEW_7pV92eONcRnus-2zmdrHPtmx5wHYadMj1IcseDOFrzVDjl9yXMw--5sNq5WlgiQMVI2vvOaw5BnH8Zvh0KwLM9HOqh1tOUMMfZs0xKOX0e23fn1eOv3BnUYKP2GR0NxmOgxYPIQDqxAaYWikK8dPEmgSiGJQAp1OQGtPMhPa4F6bQcR4mbgBUfzFJivGZsqExgGfHrFNWpT1hvEBOABQ6l9qh0jpjCzlwuUTuFFGsRI9dtqTJ5s3Si4zIl4Uqw6ShIV-P9b-IlrVyv8zQ3UcipqVep_-44ozt0hk144Xos069eLPn6ONruNhw8xMBsZ_A
  priority: 102
  providerName: Cold Spring Harbor Laboratory Press
Title Macrophages inhibit Coxiella burnetii by the ACOD1-itaconate pathway for containment of Q fever
URI https://www.proquest.com/docview/2662167036
https://www.biorxiv.org/content/10.1101/2022.05.10.491306
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1LT9tAEB5BIiRuQIt4aytxNXidXT8OFYJAhCqRQkWl3Kwd767Yix2C25J_z0zi0AMSR9uSZc3sfjsvfx_AqYxN6rKBjiSP0CjMfIRKVZG0OvUZOpksp3zH6e1v9WOiJ2swXv0Lw2OVK0xcALVtKq6Rn9NBksiU6aIups8Rq0Zxd3UloWE6aQX7fUExtg59gmQd96B_dTO-__VedUkKOr4W1MxJWhAU0Jd0rU5amlwISJjHk65VQeDOQTGGZvYa_n6A6sX5M9qC_r2Zutk2rLl6BzaWApLzL1DeGZbgeiJQeBGhfgoYWjFsXgPPNAnkemUbgsC5oDhPXA5_XssotASCNYWYgtWI_5m5oLhV8Mh6NxogGi8ehHe0yL_C4-jmcXgbdZIJEXKzNqLsS3MWUOTO5JikqCX6rECVUSaaM9W7NTZLqzj3A-QSjckLCuG0i41BurcLvbqp3R4IS85CtFmlMk_72htn1cBXihxok1TLffjWmaacLnkxSjZfGeuS8oql-fbhaGW0stsaL-V_Rx58_vgQNvmN3KqX8gh67eyPO6YIoMWTzq0nsD6anL0BdGetTg
linkProvider ProQuest
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1LbxMxEB6VRAhulIdoaYuR4LgidryvQ4Vo2iqlbSgoSL1ZnrWt-rIbkoU2P47_xkyygQMStx53V7K043n783wAb-XAZj4fpolkCI3GPCSodZVIl2YhRy_VGuU7ycbf9Kfr9HoLfm3uwjCscuMTV47aNRX3yN9TIFEy43FRH2bfE2aN4tPVDYWG7agV3OFqxFh3sePcL2-phFscnh3Tfr9T6vRkOhonHctAgny-mVDBknLiXBbeFqgyTCWGvESdU_FW8HR0Z12eVYMiDJG7GrYoKetJ_cBapHe07APoa-6f9KB_dDK5-vqnyaNKiparSdAqK8nz0I93J6tkCdx3UDw2lJ51SbGEc3CMzfwu_vwnMqzC3ekT6F_ZmZ9vw5avn8LDNV_l8hmYS8uMXzfkgxYi1jcRYytGzV1kCJVAbo-2MQpcCkorxcfR52OZxJZ8bk0ZrWDy41u7FJQmC0bId0gE0QTxRQRPNvUcpvchuxfQq5vavwThSDcQXV7pPJAbCdY7PQyVJn1xKkvlDrzpRGNm6zEchsVnBqmhMmYtvh3Y2wjNdJa4MH_1Zvf_n1_Do_H08sJcnE3OX8FjXp1RAlLuQa-d__D7lHy0eNBtsQBzz0r1Gx8b5lA
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1LT4NAEN5oG403n7FadU280rB0YeFoWkl91ZrUpDeyA7uRCzRt1fbfO1PQmOjBI5AsYd6PjxnGroSrA6O6viMIQiNBWQekTB2R-YFVYIRXoXyHweBF3k38yY9_YQhWCXk5W-bv6z4-AbbR-lbK7QrK1T0atYnXMkL7G3SoTN2ZZnaTNVHWJEl2POl811m8CB2WknVD888jMPStX_nLIK-9TLzLmiM9NbM9tmGKfbZVrYlcHbDkUdOirVdU_TnPi9cc8gXvlcuckEscqCq5yHMOK47RHL_uPfWFgyl_SoVxw2nn8IdecYxOOX1nDQDgpeXP3BoU5UM2jm_GvYFTL0ZwgFqyDuZYPsX6UWh0CF4AvgCrIpAK882QBrpnOlNB6oa2C1SI0WGEgZpvXK0B7x2xRlEW5pjxDFkCkKlUKovaa7XJZNemEtmUeYEvWuyyJk0yraZfJES-xPUTzB4q8rVY-4toSa0A8wT9vicCmu518o8jLtj2qB8nD7fD-1O2Q4-pQS9EmzUWszdzhn5_Aedrxn4CcwSlqA
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Macrophages+inhibit+Coxiella+burnetii+by+the+ACOD1-itaconate+pathway+for+containment+of+Q+fever&rft.jtitle=bioRxiv&rft.au=Kohl%2C+Lisa&rft.au=Alam+Siddique%2C+Nur+A&rft.au=Bodendorfer%2C+Barbara&rft.au=Berger%2C+Raffaela&rft.date=2022-05-11&rft.pub=Cold+Spring+Harbor+Laboratory+Press&rft.issn=2692-8205&rft.eissn=2692-8205&rft_id=info:doi/10.1101%2F2022.05.10.491306
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2692-8205&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2692-8205&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2692-8205&client=summon