Candice Quin, Erica N DeJong, Elina K Cook, Yi Zhen Luo, Caitlyn Vlasschaert, Sanathan Sadh, Amy Jm McNaughton, Marco M Buttigieg, Jessica A Breznik, Allison E Kennedy, Kevin Zhao, Jeffrey Mewburn, Kimberly J Dunham-Snary, Charles Ct Hindmarch, Alexander G Bick, Stephen L Archer, Michael J Rauh, Dawn Me Bowdish
Individuals with clonal hematopoiesis of indeterminate potential (CHIP) are at increased risk of aging related health conditions and all-cause mortality, but whether CHIP impacts risk of infection is much less clear. Using UK Biobank data, we revealed a positive association between CHIP and incident pneumonia in 438,421 individuals. We show that inflammation enhanced pneumonia risk, as CHIP carriers with a hypomorphic IL6 receptor polymorphism were protected. To better characterize the pathways of susceptibility, we challenged hematopoietic Tet Methylcytosine Dioxygenase 2 knockout (Tet2-/-) and floxed control mice (Tet2f/f) with Streptococcus pneumoniae...
April 4, 2024: Journal of Clinical Investigation