Malaria parasite-mediated alteration of macrophage function and increased iron availability predispose to disseminated nontyphoidal Salmonella infection

Kristen L. Lokken, Annica R. Stull-Lane, Kikkie Poels, Renee M Tsolis

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Disseminated infections with nontyphoidal Salmonella (NTS) are a significant cause of child mortality in sub-Saharan Africa. NTS infection in children is clinically associated with malaria, suggesting that malaria compromises the control of disseminated NTS infection. To study the mechanistic basis for increased NTS susceptibility, we utilized a model of concurrent infection with Salmonella enterica serotype Typhimurium and Plasmodium yoelii nigeriensis (P. yoelii). Underlying malaria blunted monocyte expression of Ly6C, a marker for inflammatory activation, and impaired recruitment of inflammatory cells to the liver. Hepatic mononuclear phagocytes expressed lower levels of inducible nitric oxide synthase, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor and showed increased levels of production of interleukin-10 and heme oxygenase-1, indicating that the underlying malaria modifies the activation state and inflammatory response of mononuclear phagocytes to NTS. P. yoelii infection also increased intracellular iron levels in liver mononuclear cells, as evidenced by elevated levels of ferritin and by the rescue of an S. Typhimurium tonB feoB mutant defective for iron uptake. In addition, concurrent P. yoelii infection partially rescued the systemic colonization defect of an S. Typhimurium spiB mutant defective for type III secretion system 2 (T3SS-2), indicating that the ability of phagocytic cells to limit the spread of S. Typhimurium is impaired during concurrent P. yoelii infection. These results show that concurrent malaria increases susceptibility to disseminated NTS infection by blunting macrophage bactericidal mechanisms and providing an essential nutrient that enhances bacterial growth.

Original languageEnglish (US)
Article numbere00301-18
JournalInfection and Immunity
Volume86
Issue number9
DOIs
StatePublished - Sep 1 2018

Keywords

  • Coinfection
  • Iron
  • Macrophage
  • Malaria
  • Salmonella

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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