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

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, Sangnae Cho, Jong Hwan Park, SungJae Shin

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1556-1567
Number of pages12
JournalInfection and Immunity
Volume83
Issue number4
DOIs
Publication statusPublished - 2015 Jan 1

Fingerprint

Toll-Like Receptor 2
Mycobacterium
Immunity
Mycobacterium Infections
Dendritic Cells
T-Lymphocytes
Lung
Neutrophil Infiltration
Interleukins
Disease Susceptibility
Infection
Interferon-gamma
Monocytes
Survival Rate
Tumor Necrosis Factor-alpha
Cytokines
Survival
Growth

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Kim, Jong Seok ; Kang, Min Jung ; Kim, Woo Sik ; Han, Seung Jung ; Kim, Hong Min ; Kim, Ho Won ; Kwon, Kee Woong ; Kim, So Jeong ; Cha, Seung Bin ; Eum, Seok Yong ; Koh, Won Jung ; Cho, Sangnae ; Park, Jong Hwan ; Shin, SungJae. / Essential engagement of toll-like receptor 2 in initiation of early protective Th1 response against rough variants of Mycobacterium abscessus. In: Infection and Immunity. 2015 ; Vol. 83, No. 4. pp. 1556-1567.
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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.",
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Kim, JS, Kang, MJ, Kim, WS, Han, SJ, Kim, HM, Kim, HW, Kwon, KW, Kim, SJ, Cha, SB, Eum, SY, Koh, WJ, Cho, S, Park, JH & Shin, S 2015, 'Essential engagement of toll-like receptor 2 in initiation of early protective Th1 response against rough variants of Mycobacterium abscessus', Infection and Immunity, vol. 83, no. 4, pp. 1556-1567. https://doi.org/10.1128/IAI.02853-14

Essential engagement of toll-like receptor 2 in initiation of early protective Th1 response against rough variants of Mycobacterium abscessus. / Kim, Jong Seok; Kang, Min Jung; Kim, Woo Sik; Han, Seung Jung; Kim, Hong Min; Kim, Ho Won; Kwon, Kee Woong; Kim, So Jeong; Cha, Seung Bin; Eum, Seok Yong; Koh, Won Jung; Cho, Sangnae; Park, Jong Hwan; Shin, SungJae.

In: Infection and Immunity, Vol. 83, No. 4, 01.01.2015, p. 1556-1567.

Research output: Contribution to journalArticle

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AU - Kim, Jong Seok

AU - Kang, Min Jung

AU - Kim, Woo Sik

AU - Han, Seung Jung

AU - Kim, Hong Min

AU - Kim, Ho Won

AU - Kwon, Kee Woong

AU - Kim, So Jeong

AU - Cha, Seung Bin

AU - Eum, Seok Yong

AU - Koh, Won Jung

AU - Cho, Sangnae

AU - Park, Jong Hwan

AU - Shin, SungJae

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