| Autor: |
Zhihong Yuan, Zohra Prasla, Frances Eun-Hyung Lee, Brahmchetna Bedi, Roy L. Sutliff, Ruxana T. Sadikot |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Pathogens, Vol 10, Iss 8, p 920 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2076-0817 |
| DOI: |
10.3390/pathogens10080920 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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