Nitric oxide brings innate immune resistance to M. tuberculosis infection among high-risk household contacts of pulmonary tuberculosis patients

PANDA, SUDHASINITIWARI, AMBRISHLUTHRA, KALPANAKUMAR, KULDEEPSINGH, ARCHANA2024-11-302024-11-302024-07PANDA SUDHASINI, TIWARI AMBRISH, LUTHRA KALPANA, KUMAR KULDEEP, SINGH ARCHANA. Nitric oxide brings innate immune resistance to M. tuberculosis infection among high-risk household contacts of pulmonary tuberculosis patients. Journal of Biosciences. 2024 Jul; 49: 1-130250-59910973-7138https://imsear.searo.who.int/handle/123456789/237870Nitric oxide (NO) and iNOS are crucial host factors in innate immunity against intracellular pathogens. However, the role of NO in Mycobacterium tuberculosis (M. tb) infection in humans remains controversial, unlike in the murine model of TB. To investigate this, levels of NO, iNOS, and L-arginine, as well as the NOS2A gene polymorphism rs57234985 at the promoter region of NOS2A, were evaluated in pulmonary TB (PTB) patients and their household contacts (HHCs). Increased levels of NO and iNOS expression in HHCs indicated exposure to M. tb infection which was confirmed by higher levels of iNOS and NO in Mantoux-positive individuals. Furthermore, higher levels of arginine were detected in HHCs, suggesting its potential role in promoting optimal NO synthesis. PTB patients had higher levels of these analytes due to ongoing active infection. Interestingly, iNOS and NO levels were inversely related to bacterial burden, suggesting their antimicrobial role. NOS2A gene polymorphism was found to be associated with disease susceptibility, with the TT genotype linked to increased iNOS expression. To conclude, iNOS plays a crucial role in controlling early M. tb infection in HHCs by inducing optimal NO production with help of L-arginine. Further longitudinal studies are needed to better understand the role of these host factors upon disease activation.Household contactsiNOSL-argininenitric oxidetuberculosisNitric oxide brings innate immune resistance to M. tuberculosis infection among high-risk household contacts of pulmonary tuberculosis patientsJournal ArticleIndiaDepartment of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Medicine, University College of Medical Sciences, New Delhi 110029, IndiaDepartment of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India