The role of IL-10 in Mycobacterium avium subsp. paratuberculosis infection

Cell Communication and Signaling - Tập 14 - Trang 1-14 - 2016
Tariq Hussain1, Syed Zahid Ali Shah1, Deming Zhao1, Srinand Sreevatsan2, Xiangmei Zhou1
1National Animal Transmissible Spongiform Encephalopathy Laboratory and key Laboratory of Animal and Zoonosis of Ministry Agriculture, College of Veterinary Medicine and State key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People’s Republic of China
2Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota, St. Paul, USA

Tóm tắt

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.

Tài liệu tham khảo

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