Rapid GPR183-mediated recruitment of eosinophils to the lung after Mycobacterium tuberculosis infection

• Published in: Cell reports (Cambridge) Vol. 40; no. 4; p. 111144
• Main Authors: Bohrer, Andrea C., Castro, Ehydel, Tocheny, Claire E., Assmann, Maike, Schwarz, Benjamin, Bohrnsen, Eric, Makiya, Michelle A., Legrand, Fanny, Hilligan, Kerry L., Baker, Paul J., Torres-Juarez, Flor, Hu, Zhidong, Ma, Hui, Wang, Lin, Niu, Liangfei, Wen, Zilu, Lee, Sang H., Kamenyeva, Olena, Kauffman, Keith D., Donato, Michele, Sher, Alan, Barber, Daniel L., Via, Laura E., Scriba, Thomas J., Khatri, Purvesh, Song, Yanzheng, Wong, Ka-Wing, Bosio, Catharine M., Klion, Amy D., Mayer-Barber, Katrin D.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 26.07.2022; Elsevier
• Subjects: alveolar macrophages; bacterial infection; CCR3; Ch25h; CP: Immunology; CP: Microbiology; eosinophils; eotaxin; GPR183; granulocytes; lung; Mycobacterium tuberculosis; neutrophils; NHP; nonhuman primate; oxysterols; rhesus macaque; granulocytes; Ch25h; rhesus macaque; oxysterols; alveolar macrophages; eosinophils; eotaxin; nonhuman primate; bacterial infection; lung; CP: Immunology; Mycobacterium tuberculosis; GPR183; NHP; CP: Microbiology; neutrophils; CCR3
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.111144

Influx of eosinophils into the lungs is typically associated with type II responses during allergy and fungal and parasitic infections. However, we previously reported that eosinophils accumulate in lung lesions during type I inflammatory responses to Mycobacterium tuberculosis (Mtb) in humans, macaques, and mice, in which they support host resistance. Here we show eosinophils migrate into the lungs of macaques and mice as early as one week after Mtb exposure. In mice this influx is CCR3 independent and instead requires cell-intrinsic expression of the oxysterol receptor GPR183, which is highly expressed on human and macaque eosinophils. Murine eosinophils interact directly with bacilli-laden alveolar macrophages, which upregulate the oxysterol-synthesizing enzyme Ch25h, and eosinophil recruitment is impaired in Ch25h-deficient mice. Our findings show that eosinophils are among the earliest cells from circulation to sense and respond to Mtb infection of alveolar macrophages and reveal a role for GPR183 in the migration of eosinophils into lung tissue. [Display omitted] •In mice and NHP, eosinophils accumulate early in Mtb-infected lungs preceding neutrophils•Eosinophils interact with Mtb-infected cells in the alveoli in mice•Early pulmonary eosinophil migration occurs independently of CCR3 in mice•Early lung migration in mice requires Ch25h and eosinophil-intrinsic GPR183 expression Eosinophils are usually associated with allergy or type II responses. Here, Bohrer et al. show that eosinophils are rapidly recruited to the lungs after respiratory infection with the intracellular pathogen Mycobacterium tuberculosis through the oxysterol sensor GPR183.