The role of IL-10 in Mycobacterium avium subsp. paratuberculosis infection
Tariq Hussain1, Syed Zahid Ali Shah1, Deming Zhao1
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, 100193, People's Republic of China.
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.
Insights
Mycobacterium avium subsp. paratuberculosis (MAP) evades host defenses by upregulating interleukin-10 (IL-10), suppressing inflammation. Targeting IL-10, MAPK, and STAT3 pathways could offer new strategies against MAP and other intracellular pathogens.
Area of Science:
- Immunology
- Microbiology
- Veterinary Medicine
Background:
- Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease in ruminants, leading to significant economic losses.
- MAP survives intracellularly within macrophages by inhibiting their antibacterial functions.
- MAP infection triggers host cell signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway, for survival.
Purpose of the Study:
- To review the role of IL-10 in early MAP infection stages.
- To elucidate the regulatory mechanisms of IL-10 dependent pathways in paratuberculosis.
- To highlight potential therapeutic targets (IL-10, MAPK, STAT3) for MAP and other intracellular pathogen infections.
Main Methods:
- Literature review focusing on MAP-host interactions and immune evasion mechanisms.
- Analysis of signaling pathways involved in MAP pathogenesis, including TLR2, MAPK, JAK/STAT.
- Examination of the role of IL-10 in modulating the host immune response to MAP.
Main Results:
- MAP infection activates TLR2, leading to MAPK-p38 activation and subsequent IL-10 upregulation.
- IL-10 signaling, via JAK/STAT3, inhibits inflammatory responses and promotes MAP survival by blocking phagosome maturation and apoptosis.
- IL-10 plays a critical role in the early stages of MAP infection, facilitating immune evasion.
Conclusions:
- IL-10 is a key mediator of immune suppression during MAP infection.
- Targeting the IL-10, MAPK, and STAT3 pathways presents a promising therapeutic strategy for paratuberculosis.
- Understanding these pathways can inform the development of novel treatments for infections caused by intracellular pathogens.
