Synergistic role of Mycobacterium indicus pranii and human beta Defensin-2 as adjunctive therapy against Mycobacterium tuberculosis

Shah Faisal; Deepak Vats; Sudhasini Panda; Vidushi Sharma; Kalpana Luthra; Anant Mohan; Savita Kulkarni; Pramod Kumar Gupta; Archana Singh

doi:10.1016/j.tube.2024.102571

Synergistic role of Mycobacterium indicus pranii and human beta Defensin-2 as adjunctive therapy against Mycobacterium tuberculosis

Tuberculosis (Edinb). 2024 Oct 15:149:102571. doi: 10.1016/j.tube.2024.102571. Online ahead of print.

Authors

Shah Faisal¹, Deepak Vats¹, Sudhasini Panda¹, Vidushi Sharma¹, Kalpana Luthra¹, Anant Mohan², Savita Kulkarni³, Pramod Kumar Gupta⁴, Archana Singh⁵

Affiliations

¹ Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India.
² Department of Pulmonary Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India.
³ Molecular Immunology and Tuberculosis Section, RMC, BARC, Mumbai, 400012, India.
⁴ Molecular Immunology and Tuberculosis Section, RMC, BARC, Mumbai, 400012, India. Electronic address: pramodbt19@gmail.com.
⁵ Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India. Electronic address: archanasingh@aiims.edu.

PMID: 39442483
DOI: 10.1016/j.tube.2024.102571

Abstract

Host-directed therapies (HDT) via modulation of specific host responses like inflammation can limit mycobacterial infection. HDTs could be included in current TB therapy as an adjunct to increase bacterial clearance and limit tissue damage to control spread. Individually, Mycobacterium indicus pranii (MIP) and human beta defensin-2 (hBD-2) are promising therapies for tuberculosis (TB). They can directly target the TB bacilli and enhance cell-mediated immune responses, which is limiting with conventional drugs. Therefore, our study investigated the combined application of MIP and hBD-2 to evaluate their efficacy in clearing infections caused by Mycobacterium smegmatis (M.smeg) and Mycobacterium tuberculosis (M.tb) (both avirulent; H37Ra and virulent strain; H37Rv) in THP-1 cells and human monocyte-derived macrophages (MDMs). A strong pro-inflammatory response was observed against the combination of MIP and hBD-2 which also correlated with a significant reduction in the bacterial load. This combination further showed protection against M.tb by enhancing pyroptosis in the infected cells. The study suggests the combined use of these potent immunomodulators, which could be employed as an effective mode of therapy as adjuvants against mycobacterial infections after validation in a suitable animal model.

Keywords: Human beta defensin-2 (hBD-2); Mycobacterium indicus pranii (MIP); Mycobacterium smegmatis (M. smeg); Mycobacterium tuberculosis (M.tb); Tuberculosis (TB).