title: Mycobacterium tuberculosisPeptidyl-Prolyl Isomerases Are Immunogenic, Alter Cytokine Profile and Aid in Intracellular Survival.
abstract: Mycobacterium tuberculosis(M. tb) has two peptidyl-prolyl isomerases (Ppiases) PpiA and PpiB, popularly known as cyclophilin A and cyclophilin B. The role of cyclophilins in processes such as signaling, cell surface recognition, chaperoning, and heat shock response has been well-documented. We present evidence thatM. tbPpiases modulate the host immune response. ELISA results revealed significant presence of antibodies toM. tbPpiases in patient sera as compared to sera from healthy individuals. Treatment of THP-1 cells with increasing concentrations of rPpiA, induced secretion of pro-inflammatory cytokines TNF-α and IL-6. Alternatively, treatment with rPpiB inhibited secretion of TNF-α and induced secretion of IL-10. Furthermore, heterologous expression ofM. tbPpiA and PpiB inMycobacterium smegmatisincreased bacterial survival in THP-1 cells as compared to those transformed with the vector control. Our results demonstrate thatM. tbPpiases are immunogenic proteins that can possibly modulate host immune response and enhance persistence of the pathogen within the host by subverting host cell generated stresses.
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of PathologyNew Delhi, India; Department of Biology, Dr. Reddy's Institute of Life Sciences, University of HyderabadHyderabad, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Pandey
authors.affiliation: Molecular Infection and Functional Biology Laboratory, Kusuma School of Biological Sciences, Indian Institute of Technology New Delhi, India.
authors.forename: Deeksha
authors.initials: D
authors.lastname: Tripathi
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of PathologyNew Delhi, India; Department of Biology, Dr. Reddy's Institute of Life Sciences, University of HyderabadHyderabad, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Khubaib
authors.affiliation: Molecular Infection and Functional Biology Laboratory, Kusuma School of Biological Sciences, Indian Institute of Technology New Delhi, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
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: Bhagwan Mahavir Medical Research Centre Hyderabad, India.
authors.forename: Gaddam
authors.initials: G
authors.lastname: Sumanlatha
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
authors.affiliation: Molecular Infection and Functional Biology Laboratory, Kusuma School of Biological Sciences, Indian Institute of TechnologyNew Delhi, India; Bhagwan Mahavir Medical Research CentreHyderabad, India; Jamia Hamdard, Institute of Molecular MedicineNew Delhi, India.
authors.forename: Seyed E
authors.initials: SE
authors.lastname: Hasnain
mesh_terms: D056704:Adaptive Immunity; D000907:Antibodies, Bacterial / Q000097:blood; D021984:Cyclophilin A / Q000378:metabolism*; D021983:Cyclophilins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D050296:Microbial Viability; D020102:Mycobacterium smegmatis / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; C081786:cyclophilin B; D021984:Cyclophilin A; D021983:Cyclophilins
keywords: M. tuberculosis; THP-1 cells; bacterial survival; cyclophilins; immune response