Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function

Kristen L. Lokken, Jason P. Mooney, Brian P. Butler, Mariana N. Xavier, Jennifer Y. Chau, Nicola Schaltenberg, Ramie H. Begum, Werner Müller, Shirley Luckhart, Renee M Tsolis

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48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere1004049
JournalPLoS Pathogens
Volume10
Issue number5
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

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    Lokken, K. L., Mooney, J. P., Butler, B. P., Xavier, M. N., Chau, J. Y., Schaltenberg, N., Begum, R. H., Müller, W., Luckhart, S., & Tsolis, R. M. (2014). Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function. PLoS Pathogens, 10(5), [e1004049]. https://doi.org/10.1371/journal.ppat.1004049