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Article: Effective clearance of intracellular Leishmania major in vivo requires pten in macrophages

TitleEffective clearance of intracellular Leishmania major in vivo requires pten in macrophages
Authors
KeywordsMacrophage
Leishmania
Pten
Issue Date2008
Citation
European Journal of Immunology, 2008, v. 38, n. 5, p. 1331-1340 How to Cite?
AbstractLeishmaniases are a major international public health problem, and macrophages are crucial for host resistance to this parasite. To determine if phosphatase and tensin homologue deleted on chromosome ten (Pten), a negative regulator of the PI3K pathway, plays a role in macrophage-mediated resistance to Leishmania, we generated C57BL/6 mice lacking Pten specifically in macrophages (LysMCrePtenflox/flox mice). Examination of lesions resulting from Leishmania major infection showed that LysMCrePtenflox/flox mice were more susceptible to the parasite than wild-type (WT) mice in the early phase of the infection, but were eventually able to eliminate the pathogen. In vitro Pten-deficient macrophages showed a reduced ability to kill parasites in response to IFN-γ treatment, possibly because the mutant cells exhibited decreased TNF secretion that correlated with reductions in inducible nitric oxide synthase expression and nitric oxide production. In response to various TLR ligands, Pten-deficient macrophages produced less TNF and IL-12 but more IL-10 than WT cells. However, analysis of cells in the lymph nodes draining L. major inoculation sites indicated that both LysMCrePtenflox/flox and WT mice developed normal Th1 responses following L. major infection, in line with the ability of LysMCrePtenflox/flox mice to eventually eliminate the parasite. Our results indicate that the efficient clearance of intracellular parasites requires Pten in macrophages. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Persistent Identifierhttp://hdl.handle.net/10722/291839
ISSN
2023 Impact Factor: 4.5
2023 SCImago Journal Rankings: 1.627
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKuroda, Shoko-
dc.contributor.authorNishio, Miki-
dc.contributor.authorSasaki, Takehiko-
dc.contributor.authorHorie, Yasuo-
dc.contributor.authorKawahara, Koichi-
dc.contributor.authorSasaki, Masato-
dc.contributor.authorNatsui, Miyuki-
dc.contributor.authorMatozaki, Takashi-
dc.contributor.authorTezuka, Hiroyuki-
dc.contributor.authorOhteki, Toshiaki-
dc.contributor.authorFörster, Irmgard-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorNakano, Toru-
dc.contributor.authorSuzuki, Akira-
dc.date.accessioned2020-11-17T14:55:13Z-
dc.date.available2020-11-17T14:55:13Z-
dc.date.issued2008-
dc.identifier.citationEuropean Journal of Immunology, 2008, v. 38, n. 5, p. 1331-1340-
dc.identifier.issn0014-2980-
dc.identifier.urihttp://hdl.handle.net/10722/291839-
dc.description.abstractLeishmaniases are a major international public health problem, and macrophages are crucial for host resistance to this parasite. To determine if phosphatase and tensin homologue deleted on chromosome ten (Pten), a negative regulator of the PI3K pathway, plays a role in macrophage-mediated resistance to Leishmania, we generated C57BL/6 mice lacking Pten specifically in macrophages (LysMCrePtenflox/flox mice). Examination of lesions resulting from Leishmania major infection showed that LysMCrePtenflox/flox mice were more susceptible to the parasite than wild-type (WT) mice in the early phase of the infection, but were eventually able to eliminate the pathogen. In vitro Pten-deficient macrophages showed a reduced ability to kill parasites in response to IFN-γ treatment, possibly because the mutant cells exhibited decreased TNF secretion that correlated with reductions in inducible nitric oxide synthase expression and nitric oxide production. In response to various TLR ligands, Pten-deficient macrophages produced less TNF and IL-12 but more IL-10 than WT cells. However, analysis of cells in the lymph nodes draining L. major inoculation sites indicated that both LysMCrePtenflox/flox and WT mice developed normal Th1 responses following L. major infection, in line with the ability of LysMCrePtenflox/flox mice to eventually eliminate the parasite. Our results indicate that the efficient clearance of intracellular parasites requires Pten in macrophages. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.-
dc.languageeng-
dc.relation.ispartofEuropean Journal of Immunology-
dc.subjectMacrophage-
dc.subjectLeishmania-
dc.subjectPten-
dc.titleEffective clearance of intracellular Leishmania major in vivo requires pten in macrophages-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/eji.200737302-
dc.identifier.pmid18398930-
dc.identifier.scopuseid_2-s2.0-47049086825-
dc.identifier.volume38-
dc.identifier.issue5-
dc.identifier.spage1331-
dc.identifier.epage1340-
dc.identifier.isiWOS:000256073400017-
dc.identifier.issnl0014-2980-

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