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- Title
Inhibition of type I interferon signaling abrogates early Mycobacterium bovis infection.
- Authors
Wang, Jie; Hussain, Tariq; Zhang, Kai; Liao, Yi; Yao, Jiao; Song, Yinjuan; Sabir, Naveed; Cheng, Guangyu; Dong, Haodi; Li, Miaoxuan; Ni, Jiamin; Mangi, Mazhar Hussain; Zhao, Deming; Zhou, Xiangmei
- Abstract
<bold>Background: </bold>Mycobacterium bovis (M. bovis) is the principal causative agent of bovine tuberculosis; however, it may also cause serious infection in human being. Type I IFN is a key factor in reducing viral multiplication and modulating host immune response against viral infection. However, the regulatory pathways of Type I IFN signaling during M. bovis infection are not yet fully explored. Here, we investigate the role of Type I IFN signaling in the pathogenesis of M. bovis infection in mice.<bold>Methods: </bold>C57BL/6 mice were treated with IFNAR1-blocking antibody or Isotype control 24 h before M. bovis infection. After 21 and 84 days of infection, mice were sacrificed and the role of Type I IFN signaling in the pathogenesis of M. bovis was investigated. ELISA and qRT-PCR were performed to detect the expression of Type I IFNs and related genes. Lung lesions induced by M. bovis were assessed by histopathological examination. Viable bacterial count was determined by CFU assay.<bold>Results: </bold>We observed an abundant expression of Type I IFNs in the 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, mediated the activation of macrophages leading to an increased pro-inflammatory profile and regulated the inflammatory cytokine production. However, no impact was observed on T cell activation and recruitment in the early acute phase of infection. Additionally, blocking of type I IFN signaling reduced bacterial burden in the infected mice as compared to untreated infected mice.<bold>Conclusions: </bold>Altogether, our results reveal that Type I IFN mediates a balance between M. bovis-mediated inflammatory reaction and host defense mechanism. Thus, modulating Type I IFN signaling could be exploited as a therapeutic strategy against a large repertoire of inflammatory disorders including tuberculosis.
- Subjects
TYPE I interferons; MYCOBACTERIUM bovis; BCG vaccines; MYCOBACTERIAL diseases; MYCOBACTERIUM avium paratuberculosis; PATHOLOGY; TUBERCULOSIS in cattle; BURULI ulcer
- Publication
BMC Infectious Diseases, 2019, Vol 19, Issue 1, pN.PAG
- ISSN
1471-2334
- Publication type
journal article
- DOI
10.1186/s12879-019-4654-3