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Severe pediatric malaria is an important risk factor for developing disseminated infections with nontyphoidalSalmonella serotypes (NTS). While recent animal studies on this subject are lacking, early work suggests that an increased risk for developing systemic NTS infection during malaria is caused by hemolytic anemia, which leads to reduced macrophage microbicidal activity. Here we established a model for oralSalmonella enterica serotype Typhimurium challenge in mice infected withPlasmodium yoelii nigeriensis . Initial characterization of this model showed that 5 days after coinoculation,P. yoelii nigeriensis infection increased the recovery ofS . Typhimurium from liver and spleen by approximately 1,000-fold. The increased bacterial burden could be only partially recapitulated by antibody-mediated hemolysis, which increased the recovery ofS . Typhimurium from liver and spleen by 10-fold. These data suggested that both hemolysis andP. yoelii nigeriensis -specific factors contributed to the increased susceptibility toS . Typhimurium. The mechanism by which hemolysis impaired resistance toS . Typhimurium was further investigated.In vitro ,S . Typhimurium was recovered 24 h after infection of hemophagocytic macrophages in 2-fold-higher numbers than after infection of mock-treated macrophages, making it unlikely that reduced macrophage microbicidal activity was solely responsible for hemolysis-induced immunosuppression during malaria. Infection withP. yoelii nigeriensis , but not antibody-mediated hemolysis, reduced serum levels of interleukin-12p70 (IL-12p70) in response toS . Typhimurium challenge. Collectively, studies establishing a mouse model for this coinfection suggest that multiple distinct malaria-induced immune defects contribute to increased susceptibility toS . Typhimurium.

infection and immunity

Both Hemolytic Anemia and Malaria Parasite-Specific Factors Increase Susceptibility to Nontyphoidal <i>Salmonella enterica</i> Serovar Typhimurium Infection in Mice

Both Hemolytic Anemia and Malaria Parasite-Specific Factors Increase Susceptibility to Nontyphoidal Salmonella enterica Serovar Typhimurium Infection in Mice