Monocyte Chemokines Enhance Atherosclerotic Plaque Necrosis After Bacterial Kidney Infection.

Cardiovascular event rate increases after acute infections, including urinary tract infections (UTI). Vascular inflammation is a major contributor to atherogenesis and plaque instability. The mechanistic pathway by which UTI impacts atherosclerosis has not been determined. Cardiovascular events were analyzed in a patient cohort, and atherosclerosis development was assessed in Ldlr mice after a pyelonephritis (PN) episode. Inflammatory gene expression profiles of murine and human atherosclerotic vessels were analyzed. Monocyte mobilization was studied by Ccr2 ablation in mice and in human primary monocytes in vitro. UTI and cardiovascular event rates are significantly associated in a propensity-score matched cohort of kidney graft recipients. Atherosclerotic aortic root plaque necrotic core area significantly increased in mice after PN. Monocyte chemotactic cytokine CCL2 was systemically elevated during healing, and its receptor CCR2 on bone marrow cells was required for increased plaque necrotic core formation, but not kidney host response or healing from PN. CCR2-mediated monocyte mobilization as demonstrated in mixed bone marrow chimeras. PN upregulated innate immune genes in the aortas during plaque development. Monocyte chemokine CCL8 was upregulated in murine atherosclerotic aorta after PN. Human CCL8 expression is associated with an inflammatory signature in human atherosclerotic plaques and systemically increased in acute human PN. As potential underlying mechanisms, CCL8 promoted human primary CCR2 monocyte migration and survival in vitro. Monocyte mobilization mediates increased atherosclerotic inflammation and plaque necrosis after bacterial kidney infection. Our data demonstrate the impact of this inflammatory pathway mediating organ interaction for enhanced cardiovascular risk.

© 2026 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

PMID: 41930659