MicroRNA-155 modulates macrophages’ response to non-tuberculous mycobacteria through COX-2/PGE2 signaling

Zhihong Yuan, Zohra Prasla, Frances Eun Hyung Lee, Brahmchetna Bedi, Roy L. Sutliff, Ruxana T. Sadikot

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Non-tuberculous mycobacteria (NTM) have been recognized as a causative agent of various human diseases, including severe infections in immunocompromised patients, such as people living with HIV. The most common species identified is the Mycobacterium avium-intracellulare complex (MAI/MAC), accounting for a majority of infections. Despite abundant information detailing the clinical significance of NTM, little is known about host-pathogen interactions in NTM infection. MicroRNAs (miRs) serve as important post-transcriptional regulators of gene expression. Using a microarray profile, we found that the expression of miR-155 and cyclo-oxygenase 2 (COX-2) is significantly increased in bone-marrow-derived macrophages from mice and human monocyte-derived macrophages from healthy volunteers that are infected with NTM. Antagomir against miR-155 effectively suppressed expression of COX-2 and reduced Prostaglandin E2(PGE2) secretion, suggesting that COX-2/PGE2 expression is dependent on miR-155. Mechanistically, we found that inhibition of NF-κB activity significantly reduced miR-155/COX-2 expression in infected macrophages. Most importantly, blockade of COX-2, E-prostanoid receptors (EP2 and EP4) enhanced killing of MAI in macrophages. These findings provide novel mechanistic insights into the role of miR-155/COX- 2/PGE2 signalling and suggest that induction of these pathways enhances survival of mycobacteria in macrophages. Defining host-pathogen interactions can lead to novel immunomodulatory therapies for NTM infections which are difficult to treat.

Original languageEnglish (US)
Article number920
JournalPathogens
Volume10
Issue number8
DOIs
StatePublished - Aug 2021
Externally publishedYes

Keywords

  • COX-2
  • MiR-155
  • Mycobacterium avium
  • Non-tuberculous mycobacteria
  • PGE2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

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