Plasmodium co-infection protects against chikungunya virus-induced pathologies

• Published in: Nature communications Vol. 9; no. 1; pp. 3905 - 13
• Main Authors: Teo, Teck-Hui, Lum, Fok-Moon, Ghaffar, Khairunnisa, Chan, Yi-Hao, Amrun, Siti Naqiah, Tan, Jeslin J. L., Lee, Cheryl Y. P., Chua, Tze-Kwang, Carissimo, Guillaume, Lee, Wendy W. L., Claser, Carla, Rajarethinam, Ravisankar, Rénia, Laurent, Ng, Lisa F. P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.09.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/2; 13/21; 13/31; 13/51; 631/250/127/1212; 631/326/596/2553; 64; 64/60; 692/699/255/1629; 692/699/255/2514; Animals; Apoptosis; Apoptosis - immunology; Arthritis - genetics; Arthritis - immunology; Arthritis - metabolism; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell migration; Chikungunya Fever - immunology; Chikungunya Fever - virology; Chikungunya virus; Chikungunya virus - immunology; Chikungunya virus - physiology; Coinfection - immunology; Coinfection - parasitology; Coinfection - virology; CXCR3 protein; Disruption; Female; Humanities and Social Sciences; Humans; Infections; Infiltration; Inflammation; Interferon-gamma - genetics; Interferon-gamma - immunology; Interferon-gamma - metabolism; Joint diseases; Lymph nodes; Lymphocytes B; Lymphocytes T; Malaria - immunology; Malaria - metabolism; Malaria - parasitology; Male; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Pathogenesis; Plasmodium; Plasmodium - immunology; Plasmodium - physiology; Science; Science (multidisciplinary); Spleen; Vector-borne diseases; Viral Load - immunology; Viremia; Viremia - immunology; Viremia - virology; Viruses; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06227-9

Co-infection with Plasmodium and chikungunya virus (CHIKV) has been reported in humans, but the impact of co-infection on pathogenesis remains unclear. Here, we show that prior exposure to Plasmodium suppresses CHIKV-associated pathologies in mice. Mechanistically, Plasmodium infection induces IFNγ, which reduces viraemia of a subsequent CHIKV infection and suppresses tissue viral load and joint inflammation. Conversely, concomitant infection with both pathogens limits the peak of joint inflammation with no effect on CHIKV viraemia. Reduced peak joint inflammation is regulated by elevated apoptosis of CD4 + T-cells in the lymph nodes and disrupted CXCR3-mediated CD4 + T-cell migration that abolishes their infiltration into the joints. Virus clearance from tissues is delayed in both infection scenarios, and is associated with a disruption of B cell affinity-maturation in the spleen that reduces CHIKV-neutralizing antibody production. Chikungunya virus (CHIKV) and Plasmodium co-infections have been reported in humans, but effects of the two pathogens on each other are unclear. Here, Teo et al. show in mice that Plasmodium infection affects CHIKV-specific T and B cell responses, leading to reduced joint inflammation.