Resumo

Corynebacterium pseudotuberculosis is an actinomyces bacterial with a great infectious potential and is the etiological agent of caseous lymphadenitis (CLA) in sheep and goats. Currently, there is no effective treatment or vaccine against this disease. The cells of the immune defense are essential to contain its spread in the host and macrophages play a key role in eliminating this bacteria. However, this action depends on how these macrophages are activated according to the external stimulus that they suffer, resulting in profiles of classical or alternative activation. The development of a mutant strain of C. pseudotuberculosis (CP13) by our research group obtained 81% protection against LCA in vivo, but still has no information on how this protection occurs. The objective of this study was to evaluate the immunological profile of macrophages in co-culture with the CP13 mutant in the parameters of cytokines TNF-α, IL-10 and TGFβ production; nitric oxide (NO), reactive oxygen species (ROS) and the enzyme arginase I production. We used primary cultures of bone marrow macrophages differentiated in co-culture with CP13 strain mutant and its parental T1. The results showed an increased production of pro-inflammatory cytokine TNF-alfa by strain T1, when compared with CP13 strain (p < 0.05) and increased production of anti-inflammatory cytokines IL-10 and TGF-beta; by CP13 strain compared with the T1 strain (p <0.05). Increased activity of the enzyme arginase I and nitric oxide production (p <0.05) when compared with control. The reactive oxygen species production was lower compared with our control (p <0.05) (Student T test). We can conclude that, in agreement with our results CP13 mutant strain can generate a profile of resistance to septic shock, for the highest induction of anti-inflammatory cytokines in a subsequent contact with virulent wild strains of C. pseudotuberculosis. This may account for the of 81% protection generated by the CP13 strain. However, he activation profile of macrophages was similar for both CP13 and T1, suggesting that the profile of mutant CP13 should induce a protection that is independent of the activation profile of macrophages.