Malaria-induced IL-10 contributes to the systemic burden of non-typhoidal Salmonella (164.10)

Abstract

Abstract Non-typhoidal Salmonella serotypes (NTS) in pediatric patients with severe malaria can develop a life threatening bacteremia, a major source of child mortality in Sub-Saharan Africa. Here, we use a mouse model, mimicking severe anemia seen in humans, to address mechanisms by which an underlying malaria infection contributes to the increased risk of NTS bacteremia. Plasmodium yoelli infected red blood cells were administered i.p. in CBA or B6 mice. At peak parasitemia, Salmonella Typhimurium was administered by g.g. 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 up to 4 days post inoculation. Our results indicate that the malaria parasite infection causes a global suppression of proinflammatory responses in the intestine, blunts intestinal neutrophil influx and increases the bacterial burden at systemic sites. Blunting of intestinal inflammatory responses was independent of antibody-induced anemia, but required induction of the immunoregulatory cytokine IL-10. Blocking IL-10 activity reduced systemic NTS in coinfected mice and administration of exogenous IL-10 was sufficient to increase the systemic burden of NTS in the absence of parasite infection. However, an increase in circulating NTS required both anemia and IL-10. Thus, we have identified two factors that synergize to increase bacteremia using a murine model.