Both Hemolytic Anemia and Malaria Parasite-Specific Factors Increase Susceptibility to NontyphoidalSalmonella entericaSerovar Typhimurium Infection in Mice
- 1 April 2010
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 78 (4), 1520-1527
- https://doi.org/10.1128/iai.00887-09
Abstract
Severe pediatric malaria is an important risk factor for developing disseminated infections with nontyphoidalSalmonellaserotypes (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 entericaserotype Typhimurium challenge in mice infected withPlasmodium yoelii nigeriensis. Initial characterization of this model showed that 5 days after coinoculation,P. yoelii nigeriensisinfection 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.Keywords
This publication has 66 references indexed in Scilit:
- Strain-specific immunity may drive adaptive polymorphism in the merozoite surface protein 1 of the rodent malaria parasite Plasmodium chabaudiInfection, Genetics and Evolution, 2009
- Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gutNature Medicine, 2008
- Production of IL-12, IL-23 and IL-27p28 by bone marrow-derived conventional dendritic cells rather than macrophages after LPS/TLR4-dependent induction by Salmonella EnteritidisImmunobiology, 2008
- Recurrent Salmonella Bacteremia in Interleukin-12 Receptor β1 DeficiencyJournal of Tropical Pediatrics, 2006
- Salmonella Bacteremia in Kenyan ChildrenThe Pediatric Infectious Disease Journal, 2006
- Use of clinical syndromes to target antibiotic prescribing in seriously ill children in malaria endemic area: observational studyBMJ, 2005
- Recurrent infections in homozygous sickle cell diseaseArchives of Disease in Childhood, 1999
- Septicemia caused by salmonella infection: An overlooked complication of sickle cell diseaseThe Journal of Pediatrics, 1997
- Cross-contamination of Plasmodium culturesParasitology Today, 1992
- Basic local alignment search toolJournal of Molecular Biology, 1990