EBI-3 Chain of IL-35 Along With TGF-β Synergistically Regulate Anti-leishmanial Immunity

Immunosuppression is a characteristic feature of chronic leishmaniasis. The dynamicity and the functional cross talks of host immune responses during Leishmania infection are still not clearly understood. Here we explored the functional aspects of accumulation of immune suppressive cellular and cyto...

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Published inFrontiers in immunology Vol. 10
Main Authors Asad, Mohammad, Sabur, Abdus, Shadab, Mohammad, Das, Sonali, Kamran, Mohd, Didwania, Nicky, Ali, Nahid
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 12.04.2019
Subjects
immune response
immune suppression
Immunology
interleukin-35
Leishmania
regulatory T cells
transforming growth factor beta
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Summary:Immunosuppression is a characteristic feature of chronic leishmaniasis. The dynamicity and the functional cross talks of host immune responses during Leishmania infection are still not clearly understood. Here we explored the functional aspects of accumulation of immune suppressive cellular and cytokine milieu during the progression of murine visceral leishmaniasis. In addition to IL-10 and TGF-β, investigation on the responses of different subunit chains of IL-12 family revealed a progressive elevation of EBI-3 and p35 chains of IL-35 with Leishmania donovani infection in BALB/c mice. The expansion of CD25 and FoxP3 positive T cells is associated with loss of IFN-γ and TNF-α response in advanced disease. Ex-vivo and in vivo neutralization of TGF-β and EBI-3 suggests a synergism in suppression of host anti-leishmanial immunity. The down-regulation of EBI-3 and TGF-β is crucial for re-activation of JAK-STAT pathway for induction as well as restoration of protective immunity against L. donovani infection.
Bibliography:This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology
Edited by: Heinrich Korner, University of Tasmania, Australia
Mohammad Shadab, Department of Pediatrics, University of Rochester Medical Center School of Medicine and Dentistry, Rochester, NY, United States
Present Address: Mohammad Asad, School of Medicine, Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, United States
Reviewed by: Werner Solbach, Universität zu Lübeck, Germany; Catherine Margaret Miller, James Cook University, Australia
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.00616