Proteasome β5i Subunit Deficiency Affects Opsonin Synthesis and Aggravates Pneumococcal Pneumonia

• Published in: PloS one Vol. 11; no. 4; p. e0153847
• Main Authors: Kirschner, Felicia, Reppe, Katrin, Andresen, Nadine, Witzenrath, Martin, Ebstein, Frédéric, Kloetzel, Peter-Michael
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2016; Public Library of Science (PLoS)
• Subjects: Animals; Antibiotics; Bacteria; Bacterial diseases; Bacterial infections; Biology and Life Sciences; Cell culture; Collectins; Cytokines; Cytokines - metabolism; Cytoplasm - metabolism; Defense mechanisms; Drug resistance; Experiments; Female; Ficolins; Flow Cytometry; Gene expression; Immune response; Immune response (humoral); Immune system; Immunity, Innate - immunology; Immunologic Factors - metabolism; Infections; Infectious diseases; Innate immunity; Interferon-gamma - metabolism; Kinases; Liver; Macrophages; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Mortality; Mutation; Neutrophils; Opsonin Proteins - metabolism; Pentraxins; Phagocytosis - physiology; Pneumonia; Pneumonia, Pneumococcal - etiology; Pneumonia, Pneumococcal - pathology; Proteasome Endopeptidase Complex - deficiency; Proteasome Endopeptidase Complex - physiology; Proteasomes; Proteins; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - immunology; Subunit structure; Transcription; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153847

Immunoproteasomes, harboring the active site subunits β5i/LMP7, β1i/LMP2, and β2i/MECL1 exert protective, regulatory or modulating functions during infection-induced immune responses. Immunoproteasomes are constitutively expressed in hematopoietic derived cells, constituting the first line of defense against invading pathogens. To clarify the impact of immunoproteasomes on the innate immune response against Streptococcus pneumoniae, we characterized the progression of disease and analyzed the systemic immune response in β5i/LMP7-/- mice. Our data show that β5i/LMP7 deficiency, which affected the subunit composition of proteasomes in murine macrophages and liver, was accompanied by reduced transcription of genes encoding immune modulating molecules such as pentraxins, ficolins, and collectins. The diminished opsonin expression suggested an impaired humoral immune response against invading pneumococci resulting in an aggravated systemic dissemination of S. pneumoniae in β5i/LMP7-/- mice. The impaired bacterial elimination in β5i/LMP7-/- mice was accompanied by an aggravated course of pneumonia with early mortality as a consequence of critical illness during the late phase of disease. In summary our results highlight an unsuspected role for immuno-subunits in modulating the innate immune response to extracellular bacterial infections.