Mycobacterium avium subsp. paratuberculosis (MAP) is an intracellular pathogen and is the causative agent of Johne's disease of domestic and wild ruminants. Johne's disease is characterized by chronic granulomatous enteritis leading to substantial economic losses to the livestock sector across the world. MAP persistently survives in phagocytic cells, most commonly in macrophages by disrupting its early antibacterial activity. MAP triggers several signaling pathways after attachment to pathogen recognition receptors (PRRs) of phagocytic cells. MAP adopts a survival strategy to escape the host defence mechanisms via the activation of mitogen-activated protein kinase (MAPK) pathway. The signaling mechanism initiated through toll like receptor 2 (TLR2) activates MAPK-p38 results in up-regulation of interleukin-10 (IL-10), and subsequent repression of inflammatory cytokines. The anti-inflammatory response of IL-10 is mediated through membrane-bound IL-10 receptors, leading to trans-phosphorylation and activation of Janus Kinase (JAK) family receptor-associated tyrosine kinases (TyKs), that promotes the activation of latent transcription factors, signal transducer and activators of transcription 3 (STAT3). IL-10 is an important inhibitory cytokine playing its role in blocking phagosome maturation and apoptosis. In the current review, we describe the importance of IL-10 in early phases of the MAP infection and regulatory mechanisms of the IL-10 dependent pathways in paratuberculosis. We also highlight the strategies to target IL-10, MAPK and STAT3 in other infections caused by intracellular pathogens.
Bibliographical noteFunding Information:
The authors declare no financial, personal, or professional conflict of interest. All authors have critically read and approved this work. We would also like to thank Prof. Paul Barrow for his useful comments before final submission of the manuscript. This work was supported by the MOST-RCUK international cooperation project (Project No. 2013DFG32500), National Natural Science Foundation of China (Project No.31572487). 2016 CAU Foreign Experts Major Projects (Project No: 2012z018). High-end Foreign Experts Recruitment Program (Project No: GDW20151100036).
© 2016 The Author(s).
- Interleukin-10 (IL-10)
- Janus Kinase (JAK)
- Mitogen-activated protein kinase (MAPK)
- Mycobacterium avium subsp. paratuberculosis (MAP)
- Signal transducer and activators of transcription-3 (STAT3)
- Toll like receptor 2 (TLR2)