IL-10 elicited during malaria infection blunts effective immune responses to non-typhoidal Salmonella (56.32)

Abstract

Abstract Co-infection of non-typhoidal Salmonella serotypes (NTS) in pediatric patients with severe Plasmodium falciparum malaria can develop a life threatening bacteremia, a major source of child mortality in Africa. Here, we use a mouse model that mimics severe anemia seen in human malaria to address mechanisms by which an underlying malaria parasite infection contributes to the increased risk of developing NTS bacteremia. Plasmodium yoelli infected red blood cells were administered intraperitoneally in CBA, B6 or B6 il10-/- mice. At peak parasitemia, Salmonella Typhimurium was administered by gavage in a streptomycin-induced colitis model. Characterization of inflammation to NTS in the cecum was assessed by histopathology, microarray and qRT-PCR. Bacterial loads in systemic tissues were followed to 4 days post infection. Our results indicate that the malaria parasite infection causes a global suppression of proinflammatory responses in the intestine, blunts the intestinal neutrophil influx normally elicited during NTS gastroenteritis and increases bacterial colonization at systemic sites. Blunting of intestinal inflammatory responses was independent of hemolytic anemia, but required induction of the immunoregulatory cytokine IL-10 by the parasites. Elimination of IL-10 activity restored intestinal inflammation in co-infected mice, and administration of recombinant IL-10 was sufficient to increase systemic colonization by S. Typhimurium in the absence of parasite infection.