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Inhibition of type I interferon signaling abrogates early Mycobacterium bovis infection.


ABSTRACT: BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Wang J 

PROVIDER: S-EPMC6894119 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Inhibition of type I interferon signaling abrogates early Mycobacterium bovis infection.

Wang Jie J   Hussain Tariq T   Zhang Kai K   Liao Yi Y   Yao Jiao J   Song Yinjuan Y   Sabir Naveed N   Cheng Guangyu G   Dong Haodi H   Li Miaoxuan M   Ni Jiamin J   Mangi Mazhar Hussain MH   Zhao Deming D   Zhou Xiangmei X  

BMC infectious diseases 20191204 1


<h4>Background</h4>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 m  ...[more]

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