2008
DOI: 10.1002/eji.200737302
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Effective clearance of intracellular Leishmania majorin vivo requires Pten in macrophages

Abstract: Leishmaniases 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 (LysMCrePten flox/flox mice). Examination of lesions resulting from Leishmania major infection showed that LysMCrePten flox/flox mic… Show more

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Cited by 29 publications
(25 citation statements)
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“…Some studies suggested PI3K contributes to NFκB activation and, thus, the inflammatory response, while induction of nitric oxide. 65 This discrepancy details the instructive role of inflammatory cytokines in an autocrine/ paracrine fashion for eliciting the effector capacity of local immune cells.…”
Section: Pathways Of Activation By Toll-like Receptorsmentioning
confidence: 99%
See 1 more Smart Citation
“…Some studies suggested PI3K contributes to NFκB activation and, thus, the inflammatory response, while induction of nitric oxide. 65 This discrepancy details the instructive role of inflammatory cytokines in an autocrine/ paracrine fashion for eliciting the effector capacity of local immune cells.…”
Section: Pathways Of Activation By Toll-like Receptorsmentioning
confidence: 99%
“…PTENdeficient macrophages secreted decreased quantities of Tnf and Il6 upon stimulation with TLR ligands. 60,64,65 Consequently, in a pneumococcal pneumonia model, mice deficient for PTEN in the myeloid compartment have less Tnf, Il6 and Cxcl1 (also known as KC), but more Il10 in their bronchiolar lavage fluid. 66 This phenotype corresponded with increased phagocytosis and elimination of intracellular bacteria by alveolar macrophages infected in vitro with Streptococcus pneumonia.…”
Section: Linking Tlr Signaling To Pi3k Activationmentioning
confidence: 99%
“…Although some evidence using pharmacological PI3K inhibition indicates that PI3K activation can promote TLR responses (4)(5)(6), the preponderance of studies with macrophages or dendritic cells from mice with genetically or pharmacologically altered PI3K activation indicates that PI3K activation negatively regulates TLR-induced proinflammatory cytokine production (7)(8)(9)(10)(11)(12). In support of a negative role for PI3K in TLR signaling, genetic deficiency in the p85α regulatory subunit of PI3K results in increased LPS-induced IL-12 production in dendritic cells (8).…”
mentioning
confidence: 99%
“…In support of a negative role for PI3K in TLR signaling, genetic deficiency in the p85α regulatory subunit of PI3K results in increased LPS-induced IL-12 production in dendritic cells (8). Additionally, genetic deficiency in lipid phosphatases that counter the activity of PI3K, such as SRC homology 2 domaincontaining inositol-5-phosphatase (SHIP) or phosphatase and tensin homolog (PTEN), results in decreased TLR responses (9,11). Although it is clear that PI3K activity is an important negative regulator of TLR responses, the exact mechanisms by which PI3K is activated after TLR ligation are still unclear.…”
mentioning
confidence: 99%
“…PI3K is an endogenous suppressor of IL-12 production triggered by TLR signaling (52). In response to various TLR ligands, PTEN-deficient Mfs produce less IL-12 than do WT cells (58).…”
Section: Discussionmentioning
confidence: 99%