The mucosal inflammatory response to non-typhoidal Salmonella in the intestine is blunted by IL-10 during concurrent malaria parasite infection

Co-infection can markedly alter the response to a pathogen, thereby changing its clinical presentation. For example, non-typhoidal Salmonella (NTS) serotypes are associated with gastroenteritis in immunocompetent individuals. In contrast, individuals with severe pediatric malaria can develop bacteremic infections with NTS, during which symptoms of gastroenteritis are commonly absent. Here, we report that in both a ligated ileal loop model and a mouse colitis model, malaria parasites caused a global suppression of gut inflammatory responses and blunted the neutrophil influx that is characteristic of NTS infection. Further, malaria parasite infection led to increased recovery of S. Typhimurium from the draining mesenteric lymph node of mice. In the mouse colitis model, blunted intestinal inflammation during NTS infection was independent of anemia, but instead required parasite-induced synthesis of IL-10. Blocking of IL-10 in co-infected mice reduced dissemination of S. Typhimurium to the mesenteric lymph node, suggesting that induction of IL-10 contributes to development of disseminated infection. Thus, IL-10 produced during the immune response to malaria in this model contributes to suppression of mucosal inflammatory responses to invasive NTS, which may contribute to differences in the clinical presentation of NTS infection in the setting of malaria.