title: Essential engagement of Toll-like receptor 2 in initiation of early protective Th1 response against rough variants of Mycobacterium abscessus.
abstract: Although Mycobacterium abscessus (M. abscessus) is becoming more prevalent in patients without overt immunodeficiency, little is known about the factors that contribute to disease susceptibility. This study was undertaken to investigate how Toll-like receptor 2 (TLR2) functionally contributes to the generation of protective immunity against M. abscessus in a morphotype-specific manner. We found that Tlr2-/- mice were extremely susceptible to an intravenous (i.v.) model of infection by M. abscessus rough variants, displaying uncontrolled infection in the lungs and a significantly lower survival rate than with wild-type (WT) mice. This uncontrolled infection resulted from failures in the following processes: (i) production of the crucial cytokines gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 12p70 (IL-12p70); (ii) early infiltration of neutrophils, monocytes, and dendritic cells (DCs) in the lungs of Tlr2-/- mice; (iii) rapid influx of CD4+ and CD8+ T cells; and (iv) the expansion of memory/effector T cells. Notably, systemic administration of M. abscessus culture filtrate-treated syngeneic DCs from WT mice greatly strengthened immune priming in vivo, resulting in a dramatic reduction in bacterial growth and improved long-term survival in Tlr2-/- mice, with a recovery of protective immunity. Our findings demonstrate that TLR2 is an essential contributor to instructive and effector immunity during M. abscessus infection in a morphotype-specific manner.
authors: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
authors: Jong-Seok
authors: JS
authors: Kim
authors: Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea.
authors: Min-Jung
authors: MJ
authors: Kang
authors: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
authors: Woo Sik
authors: WS
authors: Kim
authors: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
authors: Seung Jung
authors: SJ
authors: Han
authors: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
authors: Hong Min
authors: HM
authors: Kim
authors: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
authors: Ho Won
authors: HW
authors: Kim
authors: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
authors: Kee Woong
authors: KW
authors: Kwon
authors: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
authors: So Jeong
authors: SJ
authors: Kim
authors: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
authors: Seung Bin
authors: SB
authors: Cha
authors: Division of Immunopathology and Cellular Immunology, International Tuberculosis Research Center, Changwon, South Korea.
authors: Seok-Yong
authors: SY
authors: Eum
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Won-Jung
authors: WJ
authors: Koh
authors: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
authors: Sang-Nae
authors: SN
authors: Cho
authors: Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea jonpark@jnu.ac.kr sjshin@yuhs.ac.
authors: Jong-Hwan
authors: JH
authors: Park
authors: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea jonpark@jnu.ac.kr sjshin@yuhs.ac.
authors: Sung Jae
authors: SJ
authors: Shin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009161:Mycobacterium / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma
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