title: The role of IL-10 in Mycobacterium avium subsp. paratuberculosis infection.
abstract: 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.
authors.affiliation: National 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, 100193, People's Republic of China.
authors.forename: Tariq
authors.initials: T
authors.lastname: Hussain
authors.affiliation: National 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, 100193, People's Republic of China.
authors.forename: Syed Zahid Ali
authors.initials: SZ
authors.lastname: Shah
authors.affiliation: National 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, 100193, People's Republic of China.
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.
authors.forename: Srinand
authors.initials: S
authors.lastname: Sreevatsan
authors.affiliation: National 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, 100193, People's Republic of China. zhouxm@cau.edu.cn.
authors.forename: Xiangmei
authors.identifier: 0000-0003-1566-5745
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D053612:Janus Kinases / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D010283:Paratuberculosis / Q000235:genetics / Q000276:immunology*; D012418:Ruminants; D050791:STAT Transcription Factors / Q000276:immunology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000276:immunology
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D050791:STAT Transcription Factors; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D053612:Janus Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: 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)