Apoptosis Inhibitor of Macrophages Contributes to the Chronicity of Mycobacterium avium Infection by Promoting Foamy Macrophage Formation.

Autor:	Kajiwara C; Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo, Japan., Shiozawa A; Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo, Japan., Urabe N; Department of Respiratory Medicine, Toho University Omori Medical Center, Tokyo, Japan., Yamaguchi T; Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo, Japan., Kimura S; Faculty of Pharmaceutical Sciences, Department of Clinical Pharmacy, Shonan University of Medical Sciences, Kanagawa, Japan; and., Akasaka Y; Department of Diagnostic Pathology, Saiseikai Yokohamashi Tobu Hospital, Kanagawa, Japan., Ishii Y; Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo, Japan., Tateda K; Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo, Japan.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2023 Feb 15; Vol. 210 (4), pp. 431-441.
DOI:	10.4049/jimmunol.2200306
Abstrakt:	In Mycobacterium avium infections, macrophages play a critical role in the host defense response. Apoptosis inhibitor of macrophage (AIM), also known as CD5L, may represent a novel supportive therapy against various diseases, including metabolic syndrome and infectious diseases. The mechanisms of AIM include modulating lipid metabolism in macrophages and other host cells. We investigated the role of AIM in M. avium infections in vitro and in vivo. In a mouse model of M. avium pneumonia, foamy macrophages were induced 6 wk after infection. The bacteria localized in these macrophages. Flow cytometric analysis also confirmed that the percentage of CD11chighMHCclassIIhigh interstitial and alveolar macrophages, a cell surface marker defined as foamy macrophages, increased significantly after infection. AIM in alveolar lavage fluid and serum gradually increased after infection. Administration of recombinant AIM significantly increased the number of bacteria in the lungs of mice, accompanied by the induction of inflammatory cytokine and iNOS expression. In mouse bone marrow-derived macrophages, the mRNA expression of AIM after M. avium infection and the amount of AIM in the supernatant increased prior to the increase in intracellular bacteria. Infected cells treated with anti-AIM Abs had fewer bacteria and a higher percentage of apoptosis-positive cells than infected cells treated with isotype control Abs. Finally, AIM in the sera of patients with M. avium-pulmonary disease was measured and was significantly higher than in healthy volunteers. This suggests that AIM production is enhanced in M. avium-infected macrophages, increasing macrophage resistance to apoptosis and providing a possible site for bacterial growth. (Copyright © 2023 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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