Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function.
Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa. However, the mechanisms by which malaria contributes to increased risk of NTS bacteremia are incompletely understood. Here, we report that in a mouse co-infection model, malaria parasite infection blunts inflammatory responses to NTS, leading to decreased inflammatory pathology and increased systemic bacterial colonization. Blunting of NTS-induced inflammatory responses required induction of IL-10 by the parasites. In the absence of malaria parasite infection, administration of recombinant IL-10 together with induction of anemia had an additive effect on systemic bacterial colonization. Mice that were conditionally deficient for either myeloid cell IL-10 production or myeloid cell expression of IL-10 receptor were better able to control systemic Salmonella infection, suggesting that phagocytic cells are both producers and targets of malaria parasite-induced IL-10. Thus, IL-10 produced during the immune response to malaria increases susceptibility to disseminated NTS infection by suppressing the ability of myeloid cells, most likely macrophages, to control bacterial infection.
Department of Microbiology & Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America.
Kristen L
KL
Lokken
Department of Microbiology & Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America.
Jason P
JP
Mooney
Department of Microbiology & Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America.
Brian P
BP
Butler
Department of Microbiology & Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America; Departamento de Clínica e Cirurgia Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Mariana N
MN
Xavier
Department of Microbiology & Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America.
Jennifer Y
JY
Chau
Department of Microbiology & Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America.
Nicola
N
Schaltenberg
Department of Microbiology & Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America; Department of Life Sciences & Bioinformatics, Assam University, Diphu Campus, Karbi Anglong, Assam, India.
Ramie H
RH
Begum
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Werner
W
Müller
Department of Microbiology & Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America.
Shirley
S
Luckhart
Department of Microbiology & Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America.
Renée M
RM
Tsolis
D000818:Animals; D060085:Coinfection; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016778:Malaria, Falciparum / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000187:drug effects / Q000502:physiology*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology; D012480:Salmonella Infections / Q000150:complications* / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology; D018805:Sepsis / Q000276:immunology / Q000382:microbiology
D016753:Interleukin-10