Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable (NTHi) from Infected Lung
MicroRNAs regulate pathogen recognition pathways by modulating translation. In the immune system, miRNAs have been identified as important regulators of gene expression programs, which regulate differentiation, growth and function of innate and adaptive immune cells. Using miRNA microarray, we demonstrated that lung miRNAs were differentially expressed following non-typeable Haemophilus Influenzae (NTHi) infection in mice. To study the role of a specific miRNA in macrophages, we used antagomir (chemically modified single-stranded RNA analogues, complementary to the target miRNA) to block miRNA function. Interestingly, inhibition of microRNA-328 in mouse and human macrophages increases microbicidal activity by amplifying phagocytosis and production of reactive oxygen species. Inhibition of mR-328 in the lung enhanced bacterial clearance in mouse models of immunosuppression and emphysema. Our study provides proof of principle that miRNA pathways can be targeted in the lung and offer a potential new anti-microbial approach for the treatment of respiratory infection.
Vyšlo v časopise:
Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable (NTHi) from Infected Lung. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004549
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004549
Souhrn
MicroRNAs regulate pathogen recognition pathways by modulating translation. In the immune system, miRNAs have been identified as important regulators of gene expression programs, which regulate differentiation, growth and function of innate and adaptive immune cells. Using miRNA microarray, we demonstrated that lung miRNAs were differentially expressed following non-typeable Haemophilus Influenzae (NTHi) infection in mice. To study the role of a specific miRNA in macrophages, we used antagomir (chemically modified single-stranded RNA analogues, complementary to the target miRNA) to block miRNA function. Interestingly, inhibition of microRNA-328 in mouse and human macrophages increases microbicidal activity by amplifying phagocytosis and production of reactive oxygen species. Inhibition of mR-328 in the lung enhanced bacterial clearance in mouse models of immunosuppression and emphysema. Our study provides proof of principle that miRNA pathways can be targeted in the lung and offer a potential new anti-microbial approach for the treatment of respiratory infection.
Zdroje
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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