Humoral and cellular immune responses in mice against secreted and somatic antigens from a Corynebacterium pseudotuberculosis attenuated strain: Immune response against a C. pseudotuberculosis strain.

BACKGROUND: Corynebacterium pseudotuberculosis is the etiologic agent of caseous lymphadenitis (CL), a chronic disease that affects goats and sheep. CL is characterized by the formation of granulomas in lymph nodes and other organs, such as the lungs and liver. Current knowledge of CL pathogenesis indicates that the induction of humoral and cellular immune responses are fundamental to disease control. The aim of this study was to evaluate the humoral and cellular immune responses in BALB/c mice inoculated with a C. pseudotuberculosis strain isolated in the state of Bahia, Brazil. RESULTS: The lymphocyte proliferation and in vitro production of IFN-γ, IL-4, IL-10, IL-12 and nitric oxide by spleen cells stimulated with secreted and somatic antigens from the studied strain were evaluated. IgG subclasses were also analyzed. Results showed a significant increase of Th1-profile cytokines after 60 days post-inoculation, as well as an important humoral response, represented by high levels of IgG2a and IgG1 against C. pseudotuberculosis. CONCLUSION: The T1 strain of C. pseudotuberculosis was shown to induce humoral and cellular immune responses in BALB/c mice, but, even at a dosage of 1x10(7) CFU, no signs of the disease were observed.

MAPK involvement in cytokine production in response to Corynebacterium pseudotuberculosis infection.

BACKGROUND: Caseous lymphadenitis (CL) is a contagious infectious disease of small ruminants caused by Corynebacterium pseudotuberculosis. Is characterized by the formation of abscesses in the lymph nodes and intestines of infected animals, induced by inflammatory cytokines. The production of cytokines, such as IL-10, TNF-α, IL-4 and IFN-γ, is regulated by mitogen-activated protein kinase (MAPK) pathway activation. The present study investigated the involvement of MAPK pathways (MAPK p38, ERK 1 and ERK 2) with respect to the production of cytokines induced by antigens secreted by C. pseudotuberculosis over a 60-day course of infection. CBA mice (n = 25) were divided into three groups and infected with 102 colony forming units (CFU) of attenuated strain T1, 102 CFU of virulent strain VD57 or sterile saline solution and euthanized after 30 or 60 days. Murine splenocytes were treated with specific inhibitors (MAPK p38 inhibitor, ERK 1/2 inhibitor or ERK 2 inhibitor) and cultured with secreted antigens obtained from pathogenic bacteria (SeT1 or SeVD57). RESULTS: The MAPK pathways evaluated were observed to be involved in the production of IL-10, under stimulation by secreted antigens, while the MAPK p38 and ERK 1 pathways were shown to be primarily involved in TNF-α production. By contrast, no involvement of the MAPK p38 and ERK 1 and 2 pathways was observed in IFN-γ production, while the ERK 2 pathway demonstrated involvement in IL-4 production only in the mouse splenocytes infected with VD57 under stimulation by SeT1. CONCLUSION: The authors hypothesize that MAPK p38 and ERK 1 pathways with respect to TNF-α production, as well as the MAPK p38 and ERK 1 and 2 pathways in relation to IL-10 production under infection by C. pseudotuberculosis are important regulators of cellular response. Additionally, the lack of the MAPK p38 and ERK 1/2 pathways in IFN-γ production in infected CBA murine cells stimulated with the two secreted/excreted antigens, in IL-4 production showing involvement only via the ERK 2 pathway under stimulation by SeT1 antigen during 60-day infection period with the virulent strain, suggests that these pathways regulated the production of pro-inflammatory and regulatory cytokines in the splenic cells of CBA mice.