Essential role of IL-17A in the formation of a mycobacterial infection-induced granuloma in the lung.
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 gammadelta T cells expressing TCR Vgamma4 or Vgamma6 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 gammadelta 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 gammadelta 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 gammadelta T cells plays a critical role in the prevention of M. tuberculosis infection through the induction of mature granuloma formation.
Okamoto Yoshida
Yuko
Y
Tropical Biosphere Research Center, Division of Host Defense and Vaccinology, Department of Microbiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Umemura
Masayuki
M
Yahagi
Ayano
A
O'Brien
Rebecca L
RL
Ikuta
Koichi
K
Kishihara
Kenji
K
Hara
Hiromitsu
H
Nakae
Susumu
S
Iwakura
Yoichiro
Y
Matsuzaki
Goro
G
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006099:Granuloma / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology* / Q000472:pathogenicity; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D014774:Virulence / Q000276:immunology
D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta