MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy

Area of Science:

• Immunology
• Microbiology
• Genetics

Background:

• Leprosy exhibits a spectrum of clinical presentations linked to host immune responses, making it a model for studying human immune regulation.
• Understanding the molecular mechanisms underlying different leprosy forms, particularly immune evasion strategies employed by Mycobacterium leprae, is crucial.

Purpose of the Study:

• To identify microRNAs (miRNAs) differentially expressed in leprosy lesions.
• To elucidate the role of specific miRNAs, particularly hsa-mir-21, in Mycobacterium leprae pathogenesis and immune evasion.

Main Methods:

• Differential expression analysis of miRNAs in lesions from progressive lepromatous (L-lep) and self-limited tuberculoid (T-lep) leprosy.
• Bioinformatic analysis to identify targets of differentially expressed miRNAs.
• In vitro studies using Mycobacterium leprae-infected monocytes to assess the functional role of hsa-mir-21 on immune gene expression and antimicrobial activity.

Main Results:

• Thirteen miRNAs were found to be differentially expressed between L-lep and T-lep lesions.
• L-lep specific miRNAs, including hsa-mir-21, were enriched and targeted key immune genes downregulated in L-lep.
• Hsa-mir-21 upregulated in M. leprae-infected monocytes, downregulating TLR2/1-induced CYP27B1 and IL1B, and inhibiting vitamin D-dependent antimicrobial peptides CAMP and DEFB4A, thereby promoting M. leprae survival.

Conclusions:

• Mycobacterium leprae upregulates hsa-mir-21 to suppress the vitamin D-dependent antimicrobial pathway, facilitating immune evasion in the lepromatous form of the disease.
• Hsa-mir-21 represents a key molecular mechanism by which M. leprae manipulates host immunity to establish infection.