AUTHOR=Pandey Saurabh , Tripathi Deeksha , Khubaib Mohd , Kumar Ashutosh , Sheikh Javaid A. , Sumanlatha Gaddam , Ehtesham Nasreen Z. , Hasnain Seyed E. 

TITLE=Mycobacterium tuberculosis Peptidyl-Prolyl Isomerases Are Immunogenic, Alter Cytokine Profile and Aid in Intracellular Survival

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=7

YEAR=2017

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2017.00038

DOI=10.3389/fcimb.2017.00038

ISSN=2235-2988

ABSTRACT=<p><italic>Mycobacterium tuberculosis</italic> (<italic>M. tb</italic>) 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 that <italic>M. tb</italic> Ppiases modulate the host immune response. ELISA results revealed significant presence of antibodies to <italic>M. tb</italic> Ppiases 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 of <italic>M. tb</italic> PpiA and PpiB in <italic>Mycobacterium smegmatis</italic> increased bacterial survival in THP-1 cells as compared to those transformed with the vector control. Our results demonstrate that <italic>M. tb</italic> Ppiases 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.</p>