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. © 2014 lokken et al.