title: IFN-γ-induced macrophage antileishmanial mechanisms in mice: A role for immunity-related GTPases, Irgm1 and Irgm3, in Leishmania donovani infection in the liver.
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.
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: hwmurray@med.cornell.edu.
authors.forename: Henry W
authors.initials: HW
authors.lastname: Murray
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Marisa
authors.initials: M
authors.lastname: Mitchell-Flack
authors.affiliation: Departments of Medicine, Molecular Genetics and Microbiology and Immunology, Division of Geriatrics and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC, USA; Geriatric Research, Education and Clinical Center, VA Medical Center, Durham, NC, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Taylor
authors.affiliation: Shanghai Jiaotong University, School of Life Science and Biotechnology, Shanghai, China; Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D005260:Female; D020558:GTP Phosphohydrolases / Q000276:immunology / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000276:immunology*; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D008099:Liver / Q000201:enzymology / Q000469:parasitology / Q000473:pathology; D008109:Liver Diseases, Parasitic / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D046228:Microarray Analysis
chemical_list: D000981:Antiprotozoal Agents; C096000:Ifi1 protein, mouse; D007371:Interferon-gamma; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C101131:Igtp protein, mouse; D000967:Antimony Sodium Gluconate
keywords: Irgm1; Irgm3; Leishmania donovani; Visceral leishmaniasis