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Mycobacterium tuberculosis co-operonic PE32/PPE65 proteins alter host immune responses by hampering Th1 response

By Mohd eKhubaib, Mohd eKhubaib, Javaid Ahmad Sheikh, Saurabh ePandey, Saurabh ePandey, Battu eSrikanth, Manish eBhuwan, Nooruddin eKhan, Seyed Ehtesham Hasnain and Nasreen Zafar Ehtesham

Abstract

PE/PPE genes, present in cluster with ESAT-6 like genes, are suspected to have a role in antigenic variation and virulence of Mycobacterium tuberculosis. Their roles in immune evasion and immune modulation of host are also well documented. We present evidence that PE32/PPE65 present within the RD8 region are co-operonic, co-transcribed and co-translated, and play role in modulating host immune responses. Experiments with macrophage cell lines revealed that this protein complex suppresses pro-inflammatory cytokines such as TNF-α and IL-6 whereas also inducing high expression of anti-inflammatory IL-10. Immunization of mice with these recombinant proteins dampens an effective Th1 response as evident from reduced frequency of IFN-g and IL-2 producing CD4+ and CD8+ T cells. IgG sub-typing from serum of immunized mice revealed high levels of IgG1 when compared with IgG2a and IgG2b. Further IgG1/IgG2a ratio clearly demonstrated that the protein complex manipulates the host immune response favourable to the pathogen. Our results demonstrate that the co-transcribed and co-translated PE32 and PPE65 antigens are involved specifically in modulating anti-mycobacterial host immune response by hampering Th1 response

Topics: CD4+ T cells, CD8+ T cells, M.tuberculosis, PE32/PPE65, IgG subtyping, Microbiology, QR1-502
Publisher: Frontiers Media S.A.
Year: 2016
DOI identifier: 10.3389/fmicb.2016.00719
OAI identifier: oai:doaj.org/article:0708211c92a1414c9b78eff5412eb28e
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