Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung (original) (raw)
Journal Article
Tropical Biosphere Research Center
Division of Host Defense and Vaccinology, Department of Microbiology, Graduate School of Medicine, University of the Ryukyus
, Okinawa
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Tropical Biosphere Research Center
Division of Host Defense and Vaccinology, Department of Microbiology, Graduate School of Medicine, University of the Ryukyus
, Okinawa
Address correspondence and reprint requests to Dr. Masayuki Umemura, Molecular Microbiology Group, Department of Tropical Infectious Diseases, Tropical Biosphere Research Center, University of the Ryukyus. Senbaru 1, Nishihara, Okinawa 903-0213, Japan. E-mail address: [email protected]
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Tropical Biosphere Research Center
Division of Host Defense and Vaccinology, Department of Microbiology, Graduate School of Medicine, University of the Ryukyus
, Okinawa
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Department of Immunology, National Jewish Medical and Research Center
, Denver, CO 80206
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Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University
, Kyoto
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Division of Immunology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Nagasaki International University
, Nagasaki
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Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University
, Saga
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Frontier Research Initiative
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Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo
, Tokyo,
Japan
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Tropical Biosphere Research Center
Division of Host Defense and Vaccinology, Department of Microbiology, Graduate School of Medicine, University of the Ryukyus
, Okinawa
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Received:
16 October 2009
Accepted:
10 February 2010
Cite
Yuko Okamoto Yoshida, Masayuki Umemura, Ayano Yahagi, Rebecca L O’Brien, Koichi Ikuta, Kenji Kishihara, Hiromitsu Hara, Susumu Nakae, Yoichiro Iwakura, Goro Matsuzaki, Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung, The Journal of Immunology, Volume 184, Issue 8, April 2010, Pages 4414–4422, https://doi.org/10.4049/jimmunol.0903332
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Abstract
Granulomas play an essential role in the sequestration and killing of mycobacteria in the lung; however, the mechanisms of their development and maturation are still not clearly understood. IL-17A is involved in mature granuloma formation in the mycobacteria-infected lung. Therefore, IL-17A gene-knockout (KO) mice fail to develop mature granulomas in the Mycobacterium bovis bacille Calmette-Guérin (BCG)-infected lung. This study analyzed the mechanism of IL-17A–dependent mature granuloma formation in the mycobacteria-infected lung. The IL-17A KO mice showed a normal level of nascent granuloma formation on day 14 but failed to develop mature granulomas on day 28 after the BCG infection in the lung. The observation implies that IL-17A is required for the maturation of granuloma from the nascent to mature stage. TCR γδ T cells expressing TCR Vγ4 or Vγ6 were identified as the major IL-17A–producing cells that resided in the BCG-induced lung granuloma. The adoptive transfer of the IL-17A–producing TCR γδ T cells reconstituted granuloma formation in the IL-17A KO mice. The expression of ICAM-1 and LFA-1, which are adhesion molecules important in granuloma formation, decreased in the lung of the BCG-infected IL-17A KO mice, and their expression was induced on BCG-infected macrophages in coculture with IL-17A–producing TCR γδ T cells. Furthermore, IL-17A KO mice showed not only an impaired mature granuloma formation, but also an impaired protective response to virulent Mycobacterium tuberculosis. Therefore, IL-17A produced by TCR γδ T cells plays a critical role in the prevention of M. tuberculosis infection through the induction of mature granuloma formation.
Copyright © 2010 by The American Association of Immunologists, Inc.
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