IFN-γ-induced macrophage antileishmanial mechanisms in mice: A role for immunity-related GTPases, Irgm1 and Irgm3, in Leishmania donovani infection in the liver.

Journal Article

In C57BL/6 mice, Leishmania donovani infection in the liver provoked IFN-γ-induced expression of the immunity-related GTPases (IRG), Irgm1 and Irgm3. To gauge the antileishmanial effects of these macrophage factors in the liver, intracellular infection was analyzed in IRG-deficient mice. In early- (but not late-) stage infection, Irgm3(-/-) mice failed to properly control parasite replication, generated little tissue inflammation and were hyporesponsive to pentavalent antimony (Sb) chemotherapy. Observations limited to early-stage infection in Irgm1(-/-) mice demonstrated increased susceptibility and virtually no inflammatory cell recruitment to heavily-parasitized parenchymal foci but an intact response to chemotherapy. In L. donovani infection in the liver, the absence of either Irgm1 or Irgm3 impairs early inflammation and initial resistance; the absence of Irgm3, but not Irgm1, also appears to impair the intracellular efficacy of Sb chemotherapy.

Full Text

Duke Authors

Cited Authors

  • Murray, HW; Mitchell-Flack, M; Taylor, GA; Ma, X

Published Date

  • October 2015

Published In

Volume / Issue

  • 157 /

Start / End Page

  • 103 - 109

PubMed ID

  • 26208780

Electronic International Standard Serial Number (EISSN)

  • 1090-2449

International Standard Serial Number (ISSN)

  • 0014-4894

Digital Object Identifier (DOI)

  • 10.1016/j.exppara.2015.07.005

Language

  • eng