Host inflammatory responses to intracellular invaders: Review study

Abstract

As soon as a pathogen invades through the physical barriers of its corresponding host, host mounts a series of protective immune response to get rid of the invading pathogen. Host's pattern recognition receptors (PRR), localized at the cellular surface, cytoplasm and also in the nucleus; recognises pathogen associated molecular patterns (PAMPs) and plays crucial role in directing the immune response to be specific. Inflammatory responses are among the earliest strategies to tackle the pathogen by the host and are tightly regulated by multiple molecular pathways. Inflammasomes are multi-subunit protein complex consisting of a receptor molecule viz. NLRP3, an adaptor molecule- Apoptosis-associated speck-like protein containing a CARD (ASC) and an executioner caspase. Upon infection and/or injury; inflammasome components assemble and oligomerizes leading to the auto cleavage of the pro-caspase-1 to its active form. The activated caspase-1 cleaves immature form of the pro-inflammatory cytokines to their mature form e.g. IL1-β and IL-18 which mount inflammatory response. Moreover, C-terminal end of the Gasdermin D molecule is also cleaved by the caspase-1. The activated N-terminal Gasdermin D molecule form pores in the infected cells leading to their pyroptosis. Hence, inflammasomes drive inflammation during infection and controls the establishment of the pathogen by mounting inflammatory response and activation of the pyroptotic cell death.