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 10(2) colony forming units (CFU) of attenuated strain T1, 10(2) 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.