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Clin. Vaccine Immunol. doi:10.1128/CVI.00480-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Subcutaneous granulomas induced by Mycobacterium avium subspecies paratuberculosis vs. killed M. paratuberculosis vaccine: distinct morphology, cellular composition, and antigen presenting cell function

Immunobiology Graduate Program; Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa

^* To whom correspondence should be addressed. Email: jesseh{at}iastate.edu.

	Abstract

Type II (lepromatous) granulomas are characterized by a lack of organization with large numbers of macrophages heavily burdened with bacilli and disorganized lymphocyte infiltrations. Type II granulomas are a characteristic feature of the enteric lesions that develop during clinical M. avium subspecies paratuberculosis infection in the bovine. Considering the poor organization and function of these granulomas, it is our hypothesis that dendritic cell (DC) function within the granuloma is impaired during initial infection. In order to test our hypothesis, we used a subcutaneous M. paratuberculosis infection model to examine early DC function within M. paratuberculosis induced granulomas. In this model we first characterized the morphology, cellular composition, and cytokine profiles of subcutaneous granulomas that develop 7 days after subcutaneous inoculation with either vaccine or live M. paratuberculosis. Second, we isolated CD11⁺ cells from within granulomas and measured their maturation status and ability to induce T cell responses. Our results demonstrate that M. paratuberculosis or vaccine administration resulted in formation of distinct granulomas with unique cellular and cytokine profiles. These distinct profiles corresponded to significant differences in the phenotype and functional responses of DC from within the granulomas. Specifically the DC from the M. paratuberculosis induced granulomas had lower expression of co-stimulatory and chemokine receptors, suggesting limited maturation. This DC phenotype was associated with weaker induction of T cell proliferation. Taken together, these findings suggest that M. paratuberculosis infection in vivo influences DC function, which may shape the developing granuloma and initial local protection.