Previous Article | Next Article 
Infection and Immunity, July 2009, p. 2979-2988, Vol. 77, No. 7
0019-9567/09/$08.00+0 doi:10.1128/IAI.01411-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Mycobacterium avium subsp. paratuberculosis Fibronectin Attachment Protein Activates Dendritic Cells and Induces a Th1 Polarization 
Jun Sik Lee ,1,
,
Sung Jae Shin,2,
Michael T. Collins,3
In Duk Jung,1
Young-Il Jeong,1
Chang-Min Lee,1,
Yong Kyoo Shin,4
Daejin Kim,5 and
Yeong-Min Park1*
Department of Microbiology and Immunology, National Research Laboratory of Dendritic Cell Differentiation and Regulation, Medical Research Institute, Pusan National University, College of Medicine, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770, South Korea,1 Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea,2 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, Wisconsin 53706-1102,3 Department of Pharmacology, Chung-Ang University, College of Medicine, 211 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756, South Korea,4 Department of Anatomy, Chung-Ang University, College of Medicine, 211 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756, South Korea5
Received 18 November 2008/ Returned for modification 13 January 2009/ Accepted 29 March 2009
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-
B 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.
* Corresponding author. Mailing address: Department of Microbiology and Immunology and National Research Laboratory of Dendritic Cell Differentiation and Regulation, Medical Research Institute, College of Medicine, Pusan National University 1, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770, South Korea. Phone: 82-51-240-7557. Fax: 82-51-382-8090. E-mail: immunpym{at}pusan.ac.kr
Published ahead of print on 27 April 2009.
J.S.L. and S.J.S. contributed equally to this work.
Present address: BK21 Medical Science Education Center, College of Medicine, Pusan National University 1, Busan 602-739, South Korea.
Infection and Immunity, July 2009, p. 2979-2988, Vol. 77, No. 7
0019-9567/09/$08.00+0 doi:10.1128/IAI.01411-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»