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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00616

EB1-3 chain of IL-35 along with TGF-β synergistically regulate anti-leishmanial immunity

  • 1INFECTIOUS DISEASES AND IMMUNOLOGY, Indian Institute of Chemical Biology (CSIR), India

Immuno-suppression 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 antileishmanial 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.

Keywords: Leishmania donovani, cytokine, neutralization, depletion, Immune suppresion, immune therapy, IL-35, IL-10, IFN- γ, TGF (transforming growth factor), immune response

Received: 26 Jul 2018; Accepted: 08 Mar 2019.

Edited by:

Heinrich Korner, University of Tasmania, Australia

Reviewed by:

Werner Solbach, Universität zu Lübeck, Germany
Catherine M. Miller, James Cook University, Australia  

Copyright: © 2019 Asad, Sabur, Shadab, Kamran., DIDWANIA and ALI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. NAHID ALI, Indian Institute of Chemical Biology (CSIR), INFECTIOUS DISEASES AND IMMUNOLOGY, Kolkata, 700032, WEST BENGAL, India, nali@iicb.res.in