Affiliation:
1. Immunobiology Graduate Program
2. Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
Abstract
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
Mycobacterium avium
subsp.
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. avium
subsp.
paratuberculosis
infection model to examine early DC function within
M. avium
subsp.
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. avium
subsp.
paratuberculosis
. Second, we isolated CD11c
+
cells from within granulomas and measured their maturation status and ability to induce T-cell responses. Our results demonstrate that
M. avium
subsp.
paratuberculosis
or vaccine administration resulted in the formation of distinct granulomas with unique cellular and cytokine profiles. These distinct profiles corresponded to significant differences in the phenotypes and functional responses of DCs from within the granulomas. Specifically, the DCs from the
M. avium
subsp.
paratuberculosis
-induced granulomas had lower levels of expression of costimulatory 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. avium
subsp.
paratuberculosis
infection in vivo influences DC function, which may shape the developing granuloma and initial local protection.
Publisher
American Society for Microbiology
Subject
Microbiology (medical),Clinical Biochemistry,Immunology,Immunology and Allergy
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