CCR6 is essential for effective immunity against Mycobacterium tuberculosis infection in mice.

Tuberculosis (TB) is a global epidemic that has threatened human health throughout recorded history. TB disease, caused by infection with Mycobacterium tuberculosis (M.tb), is heterogeneous between individuals, and clinical TB outcomes are impacted by genetic and environmental risk factors. M.tb-infected individuals must maintain a careful balance of cytokines and chemokines to eliminate or contain the bacteria without causing excessive inflammation and lung damage. The CC chemokine receptor 6 (CCR6) is expressed by several immune cell populations that are classically involved in the host response to M.tb. However, the precise functions of CCR6 in the context of TB disease pathogenesis remain underexplored. Here, we show that mice lacking the CCR6 receptor (CCR6 KO) failed to restrict bacterial burden in the lungs, leading to increased dissemination compared to wild-type C57BL/6J (B6) mice, with a more pronounced effect in the lungs of females. CCR6 KO mice also developed necrotic pulmonary lesions that were phenotypically distinct from B6 mice and produced elevated levels of pro-inflammatory cytokines and chemokines at the onset of adaptive immunity, particularly IL-17. Long-term infection experiments revealed that the absence of CCR6 enhances risk for mortality following M.tb infection, particularly in females. This study provides insights into the role of CCR6 during TB pathogenesis and establishes its importance in maintaining protective immunity against M.tb within the context of a genetically tractable mouse model that forms necrotic pulmonary granulomas.

Duke Scholars

Author Clare Smith Molecular Genetics and Microbiology

Author Ashley Moseman Integrative Immunobiology