ThePatrick&WatsonLabs (@thepwlab.bsky.social)

Latest from the Watson lab-- mice carrying a mutation in mitochondrial DNA polymerase are susceptible to TB, experiencing high bacterial burdens and extensive necrosis in the lung. Yet another link between mitochondrial health and antimycobacterial immunity. journals.asm.org/doi/10.1128/...

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Necrosis drives susceptibility to Mycobacterium tuberculosis in PolgD257A mutator mice | Infection and Immunity Defects in mitochondria are associated with a variety of human diseases and metabolic disorders (1). Inherited mitochondrial diseases, caused by mutations harbored in the mitochondrial genome (mtDNA) or in nuclear-encoded mitochondrial genes, lead to devastating neurodegenerative and cardiovascular disorders (2). They are also frequently associated with chronic inflammation and autoimmunity. Type I interferonopathies, for example, are often caused by mutations that result in aberrant release of mitochondrial nucleic acids and chronic engagement of cytosolic nucleic acid sensing (3–5). Consistent with important links between mitochondrial health and immune function, patients with mitochondrial mutations are prone to frequent viral and bacterial infections that are often severe (6, 7). They can also suffer from systemic inflammatory response syndrome caused by hyperinflammation in the absence of infection (8). Furthermore, human single nucleotide polymorphisms (SNPs) in mitochondrial genes have been shown to confer susceptibility to several bacterial pathogens, including Salmonella enterica serovar Typhi (9), Listeria monocytogenes (10), and Mycobacterium leprae (11). Despite clear connections between mitochondria and immunity, the mechanistic contributions of specific mitochondrial-associated mutations in driving susceptibility to infection remain unclear. https://journals.asm.org/doi/10.1128/iai.00324-24