TLR4-mediated activation of MyD88 signaling induces protective immune response and IL-10 down-regulation in Leishmania donovani infection.

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dc.contributor.authorPaul, Joydeep
dc.contributor.authorNaskar, Kshudiram
dc.contributor.authorChowdhury, Sayan
dc.contributor.authorAlam, Md. Nur
dc.contributor.authorChakraborti, Tapati
dc.contributor.authorDe, Tripti
dc.date.accessioned2015-03-04T03:36:56Z
dc.date.available2015-03-04T03:36:56Z
dc.date.issued2014-12
dc.description.abstractIn visceral leishmaniasis, a fragmentary IL-12 driven type 1 immune response along with the expansion of IL-10 producing T-cells correlates with parasite burden and pathogenesis. Successful immunotherapy involves both suppression of IL-10 production and enhancement of IL-12 and nitric oxide (NO) production. As custodians of the innate immunity, the toll-like receptors (TLRs) constitute the first line of defense against invading pathogens. The TLR-signaling cascade initiated following innate recognition of microbes shapes the adaptive immune response. Whereas numerous studies have correlated parasite control to the adaptive response in Leishmania infection, growing body of evidence suggests that the activation of the innate immune response also plays a pivotal role in disease pathogenicity. In this study, using a TLR4 agonist, a Leishmania donovani (LD) derived 29 kDa β 1,4 galactose terminal glycoprotein (GP29), we demonstrated that the TLR adaptor myeloid differentiation primary response protein-88 (MyD88) was essential for optimal immunity following LD infection. Treatment of LD-infected cells with GP29 stimulated the production of IL-12 and NO while suppressing IL-10 production. Treatment of LD-infected cells with GP29 also induced the degradation of IKB and the nuclear translocation of NF-kB, as well as rapid phosphorylation of p38 MAPK and p54/56 JNK. Knockdown of TLR4 or MYD88 using siRNA showed reduced inflammatory response to GP29 in LD-infected cells. Biochemical inhibition of p38 MAPK, JNK or NF-kB, but not p42/44 ERK, reduced GP29-induced IL-12 and NO production in LD-infected cells. These results suggested a potential role for the TLR4-MyD88–IL-12 pathway to induce adaptive immune responses to LD infection that culminated in an effective control of intracellular parasite replication.en_US
dc.identifier.citationPaul Joydeep, Naskar Kshudiram, Chowdhury Sayan, Alam Md. Nur, Chakraborti Tapati, De Tripti. TLR4-mediated activation of MyD88 signaling induces protective immune response and IL-10 down-regulation in Leishmania donovani infection. Indian Journal of Biochemistry & Biophysics. 2014 Dec ; 51 (6): 531-541.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/156534
dc.language.isoenen_US
dc.source.urihttps://nopr.niscair.res.in/handle/123456789/30505en_US
dc.subjectInterleukin-10en_US
dc.subjectLeishmania donovanien_US
dc.subjectMitogen activated protein kinaseen_US
dc.subjectMyeloid differentiation primary response proteinen_US
dc.subjectNuclear factor kappa betaen_US
dc.subjectTh1 immune responseen_US
dc.subjectToll like receptoren_US
dc.subjectVisceral leishmaniasisen_US
dc.subject.meshAnimals
dc.subject.meshDown-Regulation --immunology
dc.subject.meshImmunity, Cellular --immunology
dc.subject.meshInterleukin-10 --immunology
dc.subject.meshLeishmania donovani --enzymology
dc.subject.meshLeishmania donovani --immunology
dc.subject.meshLeishmaniasis --immunology
dc.subject.meshLeishmaniasis --pathology
dc.subject.meshMacrophage Activation --immunology
dc.subject.meshMice
dc.subject.meshMice, Inbred BALB C
dc.subject.meshMice, Knockout
dc.subject.meshMyeloid Differentiation Factor 88 --immunology
dc.subject.meshSignal Transduction --immunology
dc.subject.meshTh1 Cells --immunology
dc.subject.meshToll-Like Receptor 4 --immunology
dc.titleTLR4-mediated activation of MyD88 signaling induces protective immune response and IL-10 down-regulation in Leishmania donovani infection.en_US
dc.typeArticleen_US
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