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TLR4-mediated activation of MyD88 signaling induces protective immune response and IL-10 down-regulation in <i style="mso-bidi-font-style:normal">Leishmania donovani</i> infection

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Title TLR4-mediated activation of MyD88 signaling induces protective immune response and IL-10 down-regulation in Leishmania donovani infection
 
Creator Paul, Joydeep
Naskar, Kshudiram
Chowdhury, Sayan
Alam, Md. Nur
Chakraborti, Tapati
De, Tripti
 
Subject Interleukin-10
Leishmania donovani
Mitogen activated protein kinase
Myeloid differentiation primary response protein
Nuclear factor kappa beta
Th1 immune response
Toll like receptor
Visceral leishmaniasis
 
Description 531-541
In 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.


 
Date 2015-02-11T04:41:00Z
2015-02-11T04:41:00Z
2014-12
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/30505
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.51(6) [December 2014]