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Essential engagement of Toll-like receptor 2 in initiation of early protective Th1 response against rough variants of Mycobacterium abscessus

Authors
 Jong-Seok Kim  ;  Min-Jung Kang  ;  Woo Sik Kim  ;  Seung Jung Han  ;  Hong Min Kim  ;  Ho Won Kim  ;  Kee Woong Kwon  ;  So Jeong Kim  ;  Seung Bin Cha  ;  Seok-Yong Eum  ;  Won-Jung Koh  ;  Sang-Nae Cho  ;  Jong-Hwan Park  ;  Sung Jae Shin 
Citation
 INFECTION AND IMMUNITY, Vol.83(4) : 1556-1567, 2015 
Journal Title
INFECTION AND IMMUNITY
ISSN
 0019-9567 
Issue Date
2015
MeSH
Animals ; Bone Marrow Cells/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Dendritic Cells/immunology ; Immunologic Memory/immunology ; Interferon-gamma/biosynthesis ; Interleukin-12/biosynthesis ; Lung/immunology ; Lung/microbiology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mycobacterium/immunology* ; Th1 Cells/immunology* ; Toll-Like Receptor 2/genetics ; Toll-Like Receptor 2/immunology* ; Tumor Necrosis Factor-alpha/biosynthesis
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.
Files in This Item:
T201501139.pdf Download
DOI
10.1128/IAI.02853-14
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Jong Seok(김종석)
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
Cho, Sang Nae(조상래)
Cha, Seung Bin(차승빈)
Han, Seung Jung(한승정)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/139949
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