AUTHOR=Theobald Sebastian J. , Müller Tony A. , Lange Dinah , Keck Katharina , Rybniker Jan 

TITLE=The role of inflammasomes as central inflammatory hubs in Mycobacterium tuberculosis infection

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1436676

DOI=10.3389/fimmu.2024.1436676

ISSN=1664-3224

ABSTRACT=<p><italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) infection represents a global health problem and is characterized by formation of granuloma with a necrotic center and a systemic inflammatory response. Inflammasomes have a crucial role in the host immune response towards <italic>Mtb</italic>. These intracellular multi-protein complexes are assembled in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Inflammasome platforms activate caspases, leading to the maturation of the proinflammatory cytokines interleukin (IL)-1 and 18 and the cleavage of gasdermin D (GSDMD), a pore-forming protein responsible for cytokine release and pyroptotic cell death. Recent <italic>in vitro</italic> and <italic>in vivo</italic> findings have highlighted the importance of inflammasome signaling and subsequent necrotic cell death in <italic>Mtb</italic>-infected innate immune cells. However, we are just beginning to understand how inflammasomes contribute to disease or to a protective immune response in tuberculosis (TB). A detailed molecular understanding of inflammasome-associated pathomechanisms may foster the development of novel host-directed therapeutics or vaccines with improved activity. In this mini-review, we discuss the regulatory and molecular aspects of inflammasome activation and the associated immunological consequences for <italic>Mtb</italic> pathogenesis.</p>