Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung
Open accessAbstract
Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.
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miR-328 augments phagocytosis and ROS production in Haemophilus influenzae infection.
“miR-328 is a key element of the host response to Haemophilus influenzae infection as it augments phagocytosis and production of ROS [173].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [173]
The Results report that inhibiting miR-328 increased NTHi phagocytosis and ROS production—the opposite of the claim that miR-328 itself augments them. One sentence in the Discussion says miR-328 acts 'by augmenting' these functions, but it conflicts with the reported experiments and the Discussion’s account of inhibition enhancing bacterial clearance. The indexed copy provides section labels but no page numbers. (LLM, conf=0.84)
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Cites
Bazzoni, F., Rossato, M., Fabbri, M., Gaudiosi, D., Mirolo, M., Mori, L., Tamassia, N., Mantovani, A., Cassatella, M. A., & Locati, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810909106 · Cited by 548 · cited 1× · see citing works
“Key examples of miRNAs that are known to be activated by pathogen associated molecular patterns (PAMPs) include miR-9 [13], miR-146 [14] and miR-155 [14], which are important in regulating inflammatory pathways in macrophages and neutrophils by controlling TLR signaling.”
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Microbiome effects on immunity, health and disease in the lung
Shukla, S. D., Budden, K. F., Neal, R., & Hansbro, P. M. (2017) · Clinical & Translational Immunology · doi:10.1038/cti.2017.6 · Cited by 287 · see citing works
Self-citationMicroRNAs as Regulators of Phagocytosis
Gierlikowski, W., & Gierlikowska, B. (2022) · Cells · doi:10.3390/cells11091380 · Cited by 25 · see citing works
- Authors
- Tay, H. L., Kaiko, G. E., Plank, M., Li, J., Maltby, S., Essilfie, A.-T., Jarnicki, A., Yang, M., Mattes, J., Hansbro, P. M., & Foster, P. S.
- Affiliations
- Hunter Medical Research Institute (AU)
- Corresponding author
- Yang, Ming
- Foster, Paul S.
- ORCID
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- PLOS Pathogens
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- Public Library of Science (PLoS)
- Published
- 2015-04-20
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- 11
- Issue
- 4
- Pages
- e1004549
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC4404141
- OpenAlex
- W2019496443
- Cited by
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- en
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- Funders
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Microbiology › Microbial infections and disease research
- Keywords
- miR-328, nontypeable Haemophilus influenzae, pulmonary infection, innate immunity, macrophages, neutrophils, phagocytosis, reactive oxygen species, microbicidal activity, bacterial clearance, steroid-induced immunosuppression, host defense
- MeSH terms
- Animals, Flow Cytometry, Fluorescent Antibody Technique, Haemophilus Infections, Haemophilus influenzae, Humans, Macrophages, Male, Mice, Inbred BALB C, Neutrophils, Respiratory Tract Infections, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, MicroRNAs, Mice
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