Related Articles Both hemolytic anemia and malaria parasite-specific factors increase susceptibility to non-typhoidal Salmonella infection in mice.

Infect Immun. 2010 Jan 25;

Authors: Roux CM, Butler BP, Chau JY, Paixao TA, Cheung KW, Santos RL, Luckhart S, Tsolis RM

Severe pediatric malaria is an important risk factor for developing disseminated infections with non-typhoidal Salmonella 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 oral S. enterica serotype Typhimurium (S. Typhimurium) challenge in mice infected with Plasmodium yoelii nigeriensis. Initial characterization of this model showed that 5 days after co-inoculation, P. y. nigeriensis infection increased recovery of S. Typhimurium from liver and spleen by approximately 1000-fold. The increased bacterial burden could only be partially recapitulated by antibody-mediated hemolysis, which increased recovery of S. Typhimurium from liver and spleen by tenfold. These data suggested that both hemolysis and P. y. nigeriensis specific factors contributed to increased susceptibility to S. Typhimurium. The mechanism by which hemolysis impaired resistance to S. Typhimurium was further investigated. In vitro, S. Typhimurium was recovered in two-fold higher numbers 24 hours after infection of hemophagocytic macrophages compared to mock-treated macrophages, making it unlikely that reduced macrophage microbicidal activity was solely responsible for hemolysis-induced immunosuppression during malaria. Infection with P. y. nigeriensis, but not antibody-mediated hemolysis, reduced serum levels of IL-12p70 in response to S. Typhimurium challenge. Collectively, studies establishing a mouse model for this co-infection suggest that multiple distinct malaria-induced immune defects contribute to increased susceptibility to S. Typhimurium.

PMID: 20100860 [PubMed - as supplied by publisher]