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

Abstract

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