Bovine tuberculosis is an important animal and zoonotic disease caused by Mycobacterium bovis. The innate immune response is the first line of defense against pathogens and is also crucial for the development of an efficient adaptive immune response. In this study we used an in vitro co-culture model of antigen presenting cells (APC) and autologous lymphocytes derived from peripheral blood mononuclear cells to identify the cell populations and immune mediators that participate in the development of an efficient innate response capable of controlling the intracellular replication of M. bovis. After M. bovis infection, bovine immune cell cultures displayed upregulated levels of iNOS, IL-22 and IFN-γ and the induction of the innate immune response was dependent on the presence of differentiated APC. Among the analyzed M. bovis isolates, only a live virulent M. bovis isolate induced an efficient innate immune response, which was increased upon stimulation of cell co-cultures with the M. bovis culture supernatant. Moreover, we demonstrated that an allelic variation of the early secreted protein ESAT-6 (ESAT6 T63A) expressed in the virulent strain is involved in this increased innate immune response. These results highlight the relevance of the compounds secreted by live M. bovis as well as the variability among the assessed M. bovis strains to induce an efficient innate immune response.

Almost 3% of the proteins of Mycobacterium tuberculosis (M. tuberculosis), the main causative agent of human tuberculosis, are lipoproteins. These lipoproteins are characteristic of the mycobacteri... Tweetable abstract Almost 3% of proteins of Mycobacterium tuberculosis, the main causative agent of human tuberculosis, are lipoproteins. This review provides an updated analysis of M. tuberculosis...

Neutrophils are the first line of defense against pathogens, combating them by using several antimicrobial mechanisms. These cells display a remarkable plasticity that can be molded by the different environments that neutrophils confront to protect the host, therefore presenting diverse phenotypes. Actually, pro- and anti-inflammatory neutrophils populations (N1- and N2-like phenotypes) have been described in cancer and inflammatory disorders. However, the identification of N1/N2 neutrophil subtypes in human intracellular bacterial diseases remains unexplored. Here, we characterized neutrophils from tuberculosis (TB) patients presenting distinct immunological status according to their disease severity. TB patients were classified as high or low responders (HR or LR) in accordance with their immunity against Mycobacterium tuberculosis (Mtb). Interestingly, by analyzing the phenotypic and functional characteristics of neutrophils from the two groups of TB patients we demonstrated that HR patient’s neutrophils display a pro-inflammatory N1-like phenotype, whereas LR patient’s neutrophils show an anti-inflammatory N2-like phenotype. Remarkably, whereas neutrophils from both groups of patients phagocytized MtbH37Rv strain equally, HR TB’s neutrophils displayed a significantly increased ability to kill pathogenic Mtb as compared to neutrophils from LR TB patients that presented a diminished capacity of bacterial elimination. Together, our findings suggest the existence of different subtypes of neutrophils in TB patients according to their immune response to Mtb and disease severity, indicating that neutrophils might be promising targets for TB host-directed therapy.