Inhibition of Type I Interferon Signaling abrogates Early Mycobacterium bovis Infection
Abstract Background: Mycobacterium bovis (M. bovis) is the central causative agent of bovine tuberculosis; however, it also caused serious infection in human beings. Type I IFNs is a key factor in reducing viral multiplication and modulate host immune defense against viral infection. However, the regulatory pathways of type I IFN signaling during Mycobactrium bovis (M. bovis) infection are not yet fully explored. Here, we investigate the role of type I IFN signaling on the pathogenesis of M. bovis infection in mice. Methods: C57BL/6 mice were treated with IFNAR1-blocking antibody or Isotype control 24 hour before M. bovis infection. After 21 and 84 days of infection mice were sacrificed, for analysis of type I IFN signaling on the pathogenesis of M. bovis. qRT-PCR and ELISA was performed to detect the expression of type I IFNs and relative gene. M. bovis induced lung lesions and viable bacterial count was assessed by conducting histopathology and CFU assay. Results: We observed an abundant expression of type I IFNs in the blood serum and lung tissues of M. bovis infected mice. In vivo blockade of type I IFN signaling reduced the recruitment of neutrophils to the lung tissue, mediate the activation of macrophages toward a pro-inflammatory profile and regulate the inflammatory cytokine production; however, no impact on T cell recruitment and activation in the early acute phase of infection was observed. Additionally, blocking of type I IFN signaling reduces bacterial burden in infected mice than untreated infected mice. Conclusions: Altogether, our results reveal that type I IFN mediates a balance between infection-mediated inflammatory reactions and pathogen’s control mechanism of the host during M. bovis infection. Thus, modulating type I IFN signaling could be exploited as therapeutic strategies against a large repertoire of inflammatory disorders, including tuberculosis.