title: Mycobacterium tuberculosis Co-operonic PE32/PPE65 Proteins Alter Host Immune Responses by Hampering Th1 Response.
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-γ 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 favorable 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.
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of PathologyNew Delhi, India; Dr. Reddy's Institute of Life Sciences, University of Hyderabad CampusHyderabad, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Khubaib
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of Pathology New Delhi, India.
authors.forename: Javaid A
authors.initials: JA
authors.lastname: Sheikh
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of PathologyNew Delhi, India; Dr. Reddy's Institute of Life Sciences, University of Hyderabad CampusHyderabad, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Pandey
authors.affiliation: Department of Biotechnology, School of Life Sciences, University of Hyderabad Hyderabad, India.
authors.forename: Battu
authors.initials: B
authors.lastname: Srikanth
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of Pathology New Delhi, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Bhuwan
authors.affiliation: Department of Biotechnology, School of Life Sciences, University of Hyderabad Hyderabad, India.
authors.forename: Nooruddin
authors.initials: N
authors.lastname: Khan
authors.affiliation: Dr. Reddy's Institute of Life Sciences, University of Hyderabad CampusHyderabad, India; Molecular Infection and Functional Biology Laboratory, Kusuma School of Biological Sciences, Indian Institute of TechnologyNew Delhi, India.
authors.forename: Seyed E
authors.initials: SE
authors.lastname: Hasnain
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of Pathology New Delhi, India.
authors.forename: Nasreen Z
authors.initials: NZ
authors.lastname: Ehtesham
keywords: CD4+ T cells; CD8+ T cells; IgG subtyping; M. tuberculosis; PE32/PPE65