Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function

• Published in: PLoS pathogens Vol. 10; no. 5; p. e1004049
• Main Authors: Lokken, Kristen L, Mooney, Jason P, Butler, Brian P, Xavier, Mariana N, Chau, Jennifer Y, Schaltenberg, Nicola, Begum, Ramie H, Müller, Werner, Luckhart, Shirley, Tsolis, Renée M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-05-2014; Public Library of Science (PLoS)
• Subjects: Analysis; Anemia; Animals; Bacterial infections; Biology and Life Sciences; Coinfection; Control; Development and progression; Diagnosis; Female; Gastroenteritis; Health aspects; Inflammation - genetics; Inflammation - immunology; Interleukin-10 - genetics; Interleukin-10 - pharmacology; Interleukin-10 - physiology; Malaria; Malaria, Falciparum - complications; Malaria, Falciparum - genetics; Malaria, Falciparum - immunology; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Mortality; Myeloid Cells - drug effects; Myeloid Cells - physiology; Parasites; Plasmodium falciparum; Plasmodium falciparum - growth & development; Plasmodium falciparum - immunology; Rodents; Salmonella; Salmonella Infections - complications; Salmonella Infections - genetics; Salmonella Infections - immunology; Salmonella Infections - microbiology; Salmonella typhimurium - growth & development; Salmonella typhimurium - immunology; Sepsis - immunology; Sepsis - microbiology; Sub-Saharan Africa
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1004049

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.