Differential responses of macrophages from bovines naturally resistant or susceptible to Mycobacterium bovis after classical and alternative activation

It is known that macrophages from naturally resistant animals possess a strong immune response against bovine tuberculosis to control mycobacterial infections. In the present study, the macrophage phagocytic activity, intracellular bacterial survival, and cytokine gene expression induced by classical and alternative activators against Mycobacterium bovis in naturally resistant or susceptible bovines, were evaluated. Animals were classified as naturally resistant or susceptible based on the capacity of their macrophages to allow M. bovis (BCG) growth. Peripheral blood macrophages from naturally resistant and susceptible animals were activated by classical and alternative stimuli and challenged with either non-pathogenic M. bovis BCG strain or pathogenic 9926 strain. Naturally resistant animals showed the highest phagocytosis index and microbial control after classical and alternative stimuli, being this response higher against the strain 9926 than the non-virulent strain. In addition, the response of macrophages activated by the classical pathway was higher than that under the alternative activation against both types of strains. Furthermore, classical pathway-activated macrophages derived from naturally resistant animals expressed higher levels of the pro-inflammatory markers iNOS, IL-1β, TNF-α, MIP-1 and MIP-3, and the anti-inflammatory markers ARGII and TGF-b, particularly to BCG. The results of this study showed that macrophages from naturally resistant animals produced stronger pro-inflammatory responses than those from susceptible ones to signals provided by classical pathway activators. Its role in innate immunity against M. bovis is yet to be determined.