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Adjuvant Activity of Mycobacterium paratuberculosis in Enhancing the Immunogenicity of Autoantigens During Experimental Autoimmune Encephalomyelitis
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Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein activates dendritic cells and induces a

Jun Sik Lee1, Sung Jae Shin, Michael T Collins

  • 1Department of Microbiology and Immunology and National Research Laboratory of Dendritic Cell Differentiation and Regulation, Medical Research Institute, College of Medicine, Pusan National University 1, Yangsan, Gyeongsangnam, South Korea.

Infection and Immunity
|April 29, 2009
PubMed

Insights

Fibronectin attachment protein (FAP) from Mycobacterium avium enhances immune responses. FAP activates dendritic cells, promoting a Th1-polarized adaptive immunity crucial for combating paratuberculosis.

Area of Science:

  • Immunology
  • Microbiology
  • Veterinary Medicine

Background:

  • Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis, is a significant economic and health concern in farmed ruminants.
  • The protective immune responses against Mycobacterium avium subsp. paratuberculosis are not well understood, despite its implications in animal and potentially human diseases (Crohn's disease).
  • Fibronectin attachment protein (FAP), a fibronectin-binding protein of Mycobacterium avium, plays a role in the pathogen's pathogenesis.

Purpose of the Study:

  • To investigate the role of Fibronectin attachment protein (FAP) in modulating both innate and adaptive immune responses to Mycobacterium avium subsp. paratuberculosis.
  • To elucidate the mechanisms by which FAP influences dendritic cell activation and T cell polarization.

Main Methods:

  • Functional characterization of FAP's effect on dendritic cell activation, including analysis of surface marker expression (CD80, CD86, MHC class I, MHC class II).
  • Assessment of FAP's impact on dendritic cell cytokine production, specifically interleukin-12 (IL-12), and its effect on T cell responses (gamma interferon production) in mixed-lymphocyte reactions.
  • Investigation of the intracellular signaling pathways (MAPK, NF-kappaB) mediating FAP's effects on dendritic cells.

Main Results:

  • FAP functionally activated dendritic cells, significantly upregulating key activation markers (CD80, CD86) and antigen-presenting molecules (MHC class I, MHC class II).
  • FAP stimulated dendritic cells to produce Th1-promoting interleukin-12, enhancing the allogeneic immunostimulatory capacity of these cells.
  • FAP treatment led to increased gamma interferon production by T cells, indicating a shift towards Th1 polarization of the adaptive immune response, mediated via MAPK and NF-kappaB pathways.

Conclusions:

  • Fibronectin attachment protein (FAP) is a key modulator of adaptive immune responses against Mycobacterium avium subsp. paratuberculosis.
  • FAP induces dendritic cell maturation and activation, driving a Th1-polarized immune response crucial for controlling mycobacterial infections.
  • Understanding FAP's immunomodulatory functions provides insights for developing novel strategies against paratuberculosis and related mycobacterial diseases.

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