Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein activates dendritic cells and induces a Th1 polarization

Sik Lee Jun, SungJae Shin, Michael T. Collins, Duk Jung In, Young Il Jeong, Chang Min Lee, Kyoo Shin Yong, Daejin Kim, Yeong Min Park

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Paratuberculosis is a chronic infectious disorder and a major problem in farmed ruminants. This disease is caused by Mycobacterium avium subsp. paratuberculosis. M. avium subsp. paratuberculosis is an important pathogen that causes Johne's disease in animals and also has been implicated as a possible cause of Crohn's disease in humans, but little is known about the protective immune responses to this microorganism. Fibronectin attachment protein (FAP) is a member of a family of fibronectin-binding proteins produced by several species of mycobacteria which is important in the pathogenesis of M. avium. Addition of recombinant FAP to human respiratory tract organ cultures inhibits M. avium binding to areas where there is epithelial damage. We characterized the role of FAP in promoting adaptive and innate immune responses. FAP functionally activated dendritic cells by augmenting the expression of CD80, CD86, major histocompatibility complex class I, and major histocompatibility complex class II. Moreover, FAP induced the allogeneic immunostimulatory capacity of dendritic cells by stimulating dendritic cell production of Th1-promoting interleukin-12. FAP also increased the production of gamma interferon by T cells in mixed-lymphocyte reactions, which would be expected to contribute to the Th1 polarization of the immune response. The expression of surface markers and cytokine production in dendritic cells was mediated by both mitogen-activated protein kinases and NF-κB pathways. These results show that FAP modulates the adaptive immune responses to M. avium subsp. paratuberculosis by inducing maturation and activation of dendritic cells, which drives Th1 polarization.

Original languageEnglish
Pages (from-to)2979-2988
Number of pages10
JournalInfection and Immunity
Volume77
Issue number7
DOIs
Publication statusPublished - 2009 Jul 1

Fingerprint

Paratuberculosis
Mycobacterium avium
Fibronectins
Dendritic Cells
Proteins
Adaptive Immunity
Major Histocompatibility Complex
Proto-Oncogene Proteins c-akt
Mixed Lymphocyte Culture Test
Organ Culture Techniques
Ruminants
Interleukin-12
Mycobacterium
Mitogen-Activated Protein Kinases
Innate Immunity
Crohn Disease
Respiratory System
Interferon-gamma
Carrier Proteins
Cytokines

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Jun, Sik Lee ; Shin, SungJae ; Collins, Michael T. ; In, Duk Jung ; Jeong, Young Il ; Lee, Chang Min ; Yong, Kyoo Shin ; Kim, Daejin ; Park, Yeong Min. / Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein activates dendritic cells and induces a Th1 polarization. In: Infection and Immunity. 2009 ; Vol. 77, No. 7. pp. 2979-2988.
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Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein activates dendritic cells and induces a Th1 polarization. / Jun, Sik Lee; Shin, SungJae; Collins, Michael T.; In, Duk Jung; Jeong, Young Il; Lee, Chang Min; Yong, Kyoo Shin; Kim, Daejin; Park, Yeong Min.

In: Infection and Immunity, Vol. 77, No. 7, 01.07.2009, p. 2979-2988.

Research output: Contribution to journalArticle

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AU - Jun, Sik Lee

AU - Shin, SungJae

AU - Collins, Michael T.

AU - In, Duk Jung

AU - Jeong, Young Il

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AU - Kim, Daejin

AU - Park, Yeong Min

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