Research Projects

Tuberculosis (TB) is an ancient disease, caused by Mycobacterium tuberculosis (Mtb). The scourge of tuberculosis disease is still borne by our society and people world over. Major reasons attributing for the challenges in control and eradication of TB are delayed diagnosis, prolonged treatment duration, lack of an effective vaccine, and emerging drug resistant Mtb strains. We are in a dire need of an effective vaccine or an effective treatment intervention during early stage of the infection. TB researchers globally as well as in India, are trying to identify early molecular drivers that accelerates the infection towards active disease. In addition to the development of a new vaccine against TB, determining and mitigation of the early risk-factors associated with progression of Mtb infection to active TB disease would be equally effective in meeting the WHO’s end TB goal by 2030. Globally, one third of the population is exposed to Mtb and harbors the bacteria in a latent form. Only 5-10% of infected individuals develop active TB disease. Latent TB infected (LTBI) individuals keep the infection in check and sustain a healthy life. This suggest that we have a robust natural immunity against Mtb. Several factors contribute to the susceptibility and development of TB disease, such as, smoking, respiratory conditions like silicosis, immunocompromised condition, malnutrition and poverty. These factors regulate the dynamicity of the immune response and often aligns with the mycobacterial strategy of immune evasion. Lately, several reports have suggested the presence of elevated levels of chemokine CCL11 in the serum of LTBI individuals and active TB patients. CCL11 along with other immune markers like CXCL10, GM-CSF, and IL-1Ra have been shown as a predictive biomarker of TB progression. Exposure to tobacco smoke recruit immature inflammatory monocytes in the lungs that provides a Mtb growth permissive niche. Interestingly, CCL11 and its receptor CCR2 mediates the recruitment of these inflammatory monocytes from the periphery to the lung. CCL11 potentially has an immune shape shifting effect on the initial response against Mtb infection. Apart from these observational studies, there has not been any mechanistic study of CCL11 chemokine in TB pathogenesis in mice model or in ccl11-/- mice model on the expression and functional kinetics of CCL11 chemokine. We hypothesize that CCL11 chemokine recruits Mtb growth permissive myeloid cells in the lung and augments disease progression. In this project, we aim to study the impact of CCL11 on early recruitment of immune cells in the lung and on granuloma development and outcome. Pharmacological intervention of CCL11 in vivo during early stage (gain/loss of function) of infection and its impact on the disease progression and outcome will be evaluated. From this study, we expect to identify potential diagnostic biomarker and therapeutic target during early stage of the infection, before granuloma initiation.