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

TitleIFN-γ-induced macrophage antileishmanial mechanisms in mice: A role for immunity-related GTPases, Irgm1 and Irgm3, in Leishmania donovani infection in the liver.
Publication TypeJournal Article
Year of Publication2015
AuthorsMurray HW, Mitchell-Flack M, Taylor GA, Ma X
JournalExp Parasitol
Volume157
Pagination103-9
Date Published2015 Oct
ISSN1090-2449
KeywordsAnimals, Antimony Sodium Gluconate, Antiprotozoal Agents, Female, Gene Expression Regulation, GTP Phosphohydrolases, GTP-Binding Proteins, Interferon-gamma, Leishmania donovani, Leishmaniasis, Visceral, Liver, Liver Diseases, Parasitic, Macrophages, Mice, Microarray Analysis
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.

DOI10.1016/j.exppara.2015.07.005
Alternate JournalExp Parasitol
PubMed ID26208780
PubMed Central IDPMC4640457
Grant ListR01 AI083219 / AI / NIAID NIH HHS / United States
5R01AI083219 / AI / NIAID NIH HHS / United States
R01AI57831 / AI / NIAID NIH HHS / United States
R01 AI057831 / AI / NIAID NIH HHS / United States
I01 BX002369 / BX / BLRD VA / United States

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