Regulation of Expression of Major Histocompatibility Antigens by Bovine Macrophages Infected withMycobacterium aviumsubsp.paratuberculosisorMycobacterium aviumsubsp.avium

Abstract

Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium are antigenically and genetically very similar organisms; however, they differ markedly in their virulence for cattle. We evaluated the capacity of bovine macrophages infected with M. avium subsp. paratuberculosis or M. avium subsp. avium to express major histocompatibility complex (MHC) class I and class II antigens on their surface and to interact with primed autologous lymphocytes. Our results indicate that infection of bovine macrophages with M. avium subsp. paratuberculosis promoted the downregulation of MHC class I and class II molecules on the macrophage surface within 24 and 12 h, respectively. Alternatively, MHC class II expression by M. avium subsp. aviuminfected macrophages was not detected until 24 h after infection, and the magnitude of the decrease was smaller. Decreased MHC class I expression by M. avium subsp. avium-infected macrophages was not detected. Unlike M. avium subsp. paratuberculosis-infected macrophages, M. avium subsp. avium-infected macrophages upregulated MHC class I and class II expression after activation by gamma interferon or tumor necrosis factor alpha. Further, M. avium subsp. avium-infected macrophages were lysed by primed autologous lymphocytes, whereas M. avium subsp. paratuberculosis-infected macrophages were not. Overall, the results support the hypothesis that the difference in the virulence of M. avium subsp. paratuberculosis and M. avium subsp. avium for cattle is dependent on a difference in the capacity of the organisms to suppress mycobacterial antigen presentation to T lymphocytes.

Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities

“…There are many examples of this: the downregulation of major histocompatibility complex class I and II molecules in Mycobacterium avium subsp. paratuberculosis-infected bovine macrophages (74), the hyporesponsiveness in ileal lymphocytes from Mycobacterium avium subsp. paratuberculosis-infected cows (75), abnormalities in the regulation of cytokine expression (9,13,16,30,31,65,73), the perturbation of macrophage activation and apoptosis (13,15), and the impairment of nitric oxide responsiveness (61 (33,35,68).…”

“…Mycobacterium avium subsp. paratuberculosis infection in cases of Johne's disease is associated with a chronic enteric neuritis (6,29), together with immune activation and dysregulation (15,16,61,65,74,75).…”

Differential Responses of Bovine Macrophages toMycobacterium aviumsubsp.paratuberculosisandMycobacterium aviumsubsp.avium

“…Blood was centrifuged, and the buffy coat was removed. Peripheral blood mononuclear cells were isolated by use of Percoll (58%) density gradient centrifugation, washed, and resuspended at 10 7 cells/ml (32). For preparation of monocyte-derived macrophages, 10 7 mononuclear cells were allowed to adhere to a 25-mm plastic tissue culture plate for 90 min, and nonadherent cells were washed off.…”

Bovine Immunoinhibitory Receptors Contribute to Suppression of Mycobacterium avium subsp. paratuberculosis-Specific T-Cell Responses

“…paratuberculosis infection inhibits phagocytic maturation of macrophages (35), downregulates MHC class I and II molecules (31), and induces interleukin-10 (IL-10) production (36), resulting in immune evasion and bacterial persistence. Accordingly, PD-L1 was upregulated on circulating macrophages and localized to M. avium subsp.…”