Impact of anti TB drugs on modulations of T cell receptor mediated signalling events in TB Pleurisy patients

Bhawna Sharma^1*Beenu Joshi¹Santosh Kumar²

• ¹ICMR - National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, India
• ²SN Medical College, Agra, India

Immunity in tuberculosis (TB) infection is complex as Mycobacterium tuberculosis (MTB) is a highly adaptive pathogen and may escape the immune defense through various ways. During MTB infection, immune modulation involves the activation and regulation of various immune cells and signaling pathways to mount an effective defense against the pathogen, while minimizing immune pathology. Host pathogen interactions in TB are complex as MTB is a pathogen that can able to adapt, survive and may escape the immune defense through various ways. The limitations of BCG vaccine have energized researchers to identify alternative vaccines for TB. For the rational design of new efficacious and safe vaccines against TB, advanced knowledge of protective and pathological immune responses in TB is needed. It has been well established that the existing anti-TB treatment (ATT), induced enhanced production of IL-2 and IFN-γ by T cells. This study explores modulations in the activation/phosphorylation of T cell signalling molecules in the peripheral blood of TBP patients following 6 months of treatment. We reviewed existing evidence on TCR signaling alterations in TB and propose mechanisms by which treatment influences activation of intracellular calcium mobilization, ZAP-70, PKC-theta and MAPK activation which is finally impacting T-cell function by regulating production of cytokines and impacting immune control of MTB. Our findings suggest that while treatment reduces bacterial burden, residual immune dysregulation in T cell activation pathways may persist, influencing long-term T-cell responses. Further studies are needed to fully elucidate these changes and their implications for relapse prevention and therapeutic strategies.