Kumari Lab

Host cells are equipped with several pattern recognition receptors strategically located at different locations–cell surface, endosomes, cytosol etc–for robust microbial surveillance. Downstream to microbial detection a tug-of-war between host and pathogen occurs and outcome of this host-pathogen interaction decides microbial clearance (host wins) or infection establishment (microbe wins). We explore the host and microbial factors that directly contribute to this tug-of-war and its outcome to understand the mechanisms of infectious diseases.

Different cells in hosts are specialized to perform different functions for the overall wellbeing of the body. During microbial invasion, hematopoietic cells are known to contribute majorly to combat the infection and maintain homeostasis in the host body. However, the global nature of infection enables them to interact with several other type of host cells too. However, our understanding of microbial interactions with non-hematopoietic cells for establishing infection and diseases is limited.  We explore the hierarchical contribution of hematopoietic and non-hematopoietic cells in infectious diseases.

Lipopolysaccharide (LPS) is an outer membrane molecule of Gram-negative bacteria which famously acts as a pathogen-associated molecular pattern (PAMP) during interactions with host. Cytosolic invasion of LPS is sensed by the inflammatory PRR, caspases-4/11 which activates a pore forming protein gasdermin D (GSDMD). GSDMD pores allow passive release of intracellular molecules that contribute to host immune responses against pathogenic attack and cell death if remains unchecked. This type of cell death induces systemic inflammation and hence called Pyro (firey)-ptosis (death) "pyroptosis". Whereas body's immune system is regulated by several complex signaling pathways, the cytosolic LPS sensing pathway appears relatively less complex and exists in variety of hematopoietic and non-hematopoietic cells which creates a wider coverage for LPS-sensing across the body. We are interested in exploring role of LPS–whether derived from external infection or gut-leakage–in causing infectious and metabolic diseases.