CCL5 participates in early protection against Mycobacterium tuberculosis

Journal of Leukocyte Biology

Joanne Turner¹  Bridget Vesosky³  Gillian Beamer²  Erin K. Rottinghaus³  Paul Stromberg⁴ 

[1] Center for Microbial Interface Biology and Departments of Internal Medicine, Division of Infectious Diseases, The Ohio State University, Columbus, Ohio, USA Center for Microbial Interface Biology and Departments of Center for Microbial Interface Biology and Departments of Internal Medicine, Division of Infectious Diseases, The Ohio State University, Columbus, Ohio, USA Internal Medicine, Division of Infectious Diseases, The Ohio State University, Columbus, Ohio, USA Center for Microbial Interface Biology and Departments of Internal Medicine, Division of Infectious Diseases, The Ohio State University, Columbus, Ohio, USA;Center for Microbial Interface Biology and Departments of Veterinary Biosciences and Center for Microbial Interface Biology and Departments of Center for Microbial Interface Biology and Departments of Veterinary Biosciences and Veterinary Biosciences and Center for Microbial Interface Biology and Departments of Veterinary Biosciences and;Center for Microbial Interface Biology and Departments of Center for Microbial Interface Biology and Departments of Center for Microbial Interface Biology and Departments of;Veterinary Biosciences and Veterinary Biosciences and Veterinary Biosciences and

关键词: chemokine;    granuloma;    pulmonary;    murine;   

DOI  :  10.1189/jlb.1109742

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Control of M.tb, the causative agent of TB, requires immune cell recruitment to form lung granulomas. The chemokines and chemokine receptors that promote cell migration for granuloma formation, however, are not defined completely. As immunity to M.tb manifests slowly in the lungs, a better understanding of specific roles for chemokines, in particular those that promote M.tb-protective TH1 responses, may identify targets that could accelerate granuloma formation. The chemokine CCL5 has been detected in patients with TB and implicated in control of M.tb infection. To define a role for CCL5 in vivo during M.tb infection, CCL5 KO mice were infected with a low dose of aerosolized M.tb. During early M.tb infection, CCL5 KO mice localized fewer APCs and chemokine receptor-positive T cells to the lungs and had microscopic evidence of altered cell trafficking to M.tb granulomas. Early acquired immunity and granuloma function were transiently impaired when CCL5 was absent, evident by delayed IFN-γ responses and poor control of M.tb growth. Lung cells from M.tb-infected CCL5 KO mice eventually reached or exceeded the levels of WT mice, likely as a result of partial compensation by the CCL5-related ligand, CCL4, and not because of CCL3. Finally, our results suggest that most T cells use CCR5 but not CCR1 to interact with these ligands. Overall, these results contribute to a model of M.tb granuloma formation dependent on temporal regulation of chemokines rather than on redundant or promiscuous interactions.

【 授权许可】

Unknown