IL-27 Suppresses Antimicrobial Activity in Human Leprosy

Area of Science:

• Immunology
• Microbiology
• Pathogenesis of Infectious Diseases

Background:

• Intracellular pathogens evade host defenses via immunosuppressive pathways.
• Type I interferons (IFN) and Interleukin-10 (IL-10) are implicated in inhibiting host responses, but the mechanism remains unclear.
• Gene expression in leprosy lesions suggests a link between IL-27 and IFN-induced IL-10.

Purpose of the Study:

• To elucidate the role of IL-27 in the IFN-β induced IL-10 pathway during Mycobacterium leprae infection.
• To investigate the functional impact of IL-27 on host antimicrobial responses in leprosy.
• To examine the expression and localization of IL-27 in leprosy skin lesions.

Main Methods:

• Monocyte cultures treated with IFN-β and Mycobacterium leprae.
• IL-27 knockdown experiments.
• Recombinant IL-27 treatment of monocytes.
• Assessment of IFN-γ-mediated antimicrobial activity.
• Immunohistochemical analysis of patient skin lesions.

Main Results:

• IFN-β and M. leprae upregulate IL-27p28 in monocytes, which is critical for IL-10 induction.
• IL-27 knockdown diminishes IFN-β and M. leprae-induced IL-10 production.
• Recombinant IL-27 directly induces IL-10 production in monocytes.
• IL-27 suppresses IFN-γ's antimicrobial activity against M. leprae.
• IL-27 expression correlates with IFN-β and IL-10 in macrophages within leprosy lesions.

Conclusions:

• IL-27 is a key mediator in the IFN-β induced IL-10 pathway during M. leprae infection.
• IL-27 contributes to immunosuppression by inhibiting host antimicrobial responses in leprosy.
• IL-27 plays a significant role in the human cutaneous immune response to microbial infections like leprosy.