1. IFN-γ-induced macrophage antileishmanial mechanisms in mice: A role for immunity-related GTPases, Irgm1 and Irgm3, in Leishmania donovani infection in the liver.
- Author
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Murray HW, Mitchell-Flack M, Taylor GA, and Ma X
- Subjects
- Animals, Antimony Sodium Gluconate therapeutic use, Antiprotozoal Agents therapeutic use, Female, GTP Phosphohydrolases immunology, GTP-Binding Proteins immunology, Gene Expression Regulation, Leishmaniasis, Visceral drug therapy, Leishmaniasis, Visceral enzymology, Liver enzymology, Liver parasitology, Liver pathology, Liver Diseases, Parasitic drug therapy, Liver Diseases, Parasitic enzymology, Macrophages immunology, Mice, Microarray Analysis, GTP Phosphohydrolases metabolism, GTP-Binding Proteins metabolism, Interferon-gamma immunology, Leishmania donovani immunology, Leishmaniasis, Visceral immunology, Liver Diseases, Parasitic immunology
- Abstract
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., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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