Abhishek Mishra, PhD

Tuberculosis (TB) is one of the deadliest infectious diseases, caused by Mycobacterium tuberculosis (Mtb), accounts for more than 1.7 million deaths every year (WHO Report 2023). A characteristic feature of pulmonary tuberculosis is granuloma, which is the collection of immune cells and mesenchymal stem cells (MSCs) surrounding a central core of Mtb-infected macrophages. Granulomas restrict the growth of Mtb and continuously recruit immune and stem cells. Recent reports suggest that although MSCs are not known to interact with microbial pathogens they express Toll-like receptors (TLRs), NOD2 and RIG-I. We found that at a low dose infection Mtb persist in host stem cell for a long term without causing cell death. Interestingly, our preliminary data shows that BCG-infected MSCs reprogrammed naïve macrophages to control Mtb infection. My future research plans are focused on understanding the interaction of MSCs with innate immune cells during the Mtb infection. More specifically, my interest is to seek answers to the following questions,

1. Considering the plasticity and self-regulating nature of MSCs, it is important to find out what is the fate of infected MSCs in vivo?
2. What are the cellular processes and immune mechanisms that are responsible for the containment of Mtb infection in lung resident MSCs?
3. We know that innate immune cells are short lived. The possibility that MSCs could influence innate immune cells in the long-term is through epigenetic modifications. How do MSCs influence the innate immune cells epigenetically?

Based on the inputs from the study my goal is to develop a stem cell-based immunotherapy for TB.