Histopathological findings, phenotyping of inflammatory cells, and expression of markers of nitritative injury in joint tissue samples from calves after vaccination and intraarticular challenge with Mycoplasma bovis strain 1067

Abstract

BackgroundThe pathogenesis of caseonecrotic lesions developing in lungs and joints of calves infected with Mycoplasma bovis is not clear and attempts to prevent M. bovis-induced disease by vaccines have been largely unsuccessful. In this investigation, joint samples from 4 calves, i.e. 2 vaccinated and 2 non-vaccinated, of a vaccination experiment with intraarticular challenge were examined. The aim was to characterize the histopathological findings, the phenotypes of inflammatory cells, the expression of class II major histocompatibility complex (MHC class II) molecules, and the expression of markers for nitritative stress, i.e. inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT), in synovial membrane samples from these calves. Furthermore, the samples were examined for M. bovis antigens including variable surface protein (Vsp) antigens and M. bovis organisms by cultivation techniques.ResultsThe inoculated joints of all 4 calves had caseonecrotic and inflammatory lesions. Necrotic foci were demarcated by phagocytic cells, i.e. macrophages and neutrophilic granulocytes, and by T and B lymphocytes. The presence of M. bovis antigens in necrotic tissue lesions was associated with expression of iNOS and NT by macrophages. Only single macrophages demarcating the necrotic foci were positive for MHC class II. Microbiological results revealed that M. bovis had spread to approximately 27% of the non-inoculated joints. Differences in extent or severity between the lesions in samples from vaccinated and non-vaccinated animals were not seen.ConclusionsThe results suggest that nitritative injury, as in pneumonic lung tissue of M. bovis-infected calves, is involved in the development of caseonecrotic joint lesions. Only single macrophages were positive for MHC class II indicating down-regulation of antigen-presenting mechanisms possibly caused by local production of iNOS and NO by infiltrating macrophages.

Cellular Microbiology of Mycoplasma canis

“…This effect on cellular immunity would further contribute to general immune dysregulation by strains, such as brain isolate UFG1, that elicit comparatively low IFN-␥ or TNF-␣ responses. This pattern is consistent with DH82 cell MHC-II receptor downregulation caused by infection with the obligate intracellular canine pathogen Ehrlichia canis (36) and with the paucity of MHC-II-expressing macrophages in necrotic joint lesions of calves infected with Mycoplasma bovis by intra-articular challenge (76) but contrasts with the marked upregulation of MHC-II-expressing airway epithelial cells following intranasal inoculation of rats with Mycoplasma pulmonis (77).…”

Mycoplasma bovis-Induced Inhibition of Bovine Peripheral Blood Mononuclear Cell Proliferation Is Ameliorated after Blocking the Immune-Inhibitory Programmed Death 1 Receptor

“…surface proteins (VSPs) (4). To date, limited success is achieved in the treatment or control of disease associated with M. bovis due to its virulence and persistent nature, restrictions on antimicrobial drug usage in food animals, the emergence of drugresistant strains (5,6), and vaccination attempts that confer limited protection (7)(8)(9).…”

Recent Developments in Vaccines for Bovine Mycoplasmoses Caused by Mycoplasma bovis and Mycoplasma mycoides subsp. mycoides

“…Post-challenge, the clinical disease and the joint lesions in the vaccinated calves were similar to those observed in the non-vaccinates, which was additionally confirmed by histopathology [25,26]. To some extent, the vaccine partially reduced M. bovis joint colonization; however, it did not protect against the M. bovis spreading from the inoculated to non-inoculated joints, which was observed in both examined groups of calves [25,26]. Similar poor results were seen with another formalinized vaccine which failed to protect against M. bovis arthritis in calves [27].…”

“…The vaccine did not protect against the effects of articular challenge with the virulent M. bovis strain, despite effective stimulation of the humoral response. Post-challenge, the clinical disease and the joint lesions in the vaccinated calves were similar to those observed in the non-vaccinates, which was additionally confirmed by histopathology [25,26]. To some extent, the vaccine partially reduced M. bovis joint colonization; however, it did not protect against the M. bovis spreading from the inoculated to non-inoculated joints, which was observed in both examined groups of calves [25,26].…”

“…The use of formalin for mycoplasma cell killing in a vaccine for prevention of M. bovis -induced arthritis did not bring the expected results [ 25 , 26 ]. The vaccine did not protect against the effects of articular challenge with the virulent M. bovis strain, despite effective stimulation of the humoral response.…”