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Immunometabolic Circuits in Infection for Advancing Host Directed Therapies
Published on: September 13, 2024
MiR-155 regulates Th9 differentiation in children with methicillin-resistant Staphylococcus aureus pneumonia by
1Department of Emergency, Anhui Children's Hospital, 39 Wangjiang East Road, Baohe District, Hefei 230051, China; Department of Emergency, Anhui Medical University Affiliated Provincial Children's Hospital, Hefei 230051, China.
Insights
MicroRNA-155 (miR-155) promotes Th9 cell differentiation in children with MRSA pneumonia by targeting SIRT1. This finding reveals a novel mechanism in MRSA infection immunity.
Area of Science:
- Immunology
- Molecular Biology
- Microbiology
Background:
- Th9 cells and their primary cytokine IL-9 play a role in immune responses.
- Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) pneumonia are significant health concerns.
Purpose of the Study:
- To investigate the role of miR-155 in Th9 cell differentiation during MRSA pneumonia in children.
- To elucidate the molecular mechanism by which miR-155 influences Th9 cell differentiation in this context.
Main Methods:
- Collected bronchoalveolar lavage fluid (BALF) from children with MRSA pneumonia and controls.
- Utilized RT-PCR, ELISA, and flow cytometry to measure miR-155, IL-9, and Th9 cell numbers.
- Performed transfection experiments with miR-155 mimic/inhibitor and dual luciferase assays to identify targets.
Main Results:
- MRSA pneumonia was associated with significantly increased miR-155, IL-9, and Th9 cell numbers in BALF.
- miR-155 mimic upregulated IL-9 expression and Th9 cell differentiation, while miR-155 inhibitor decreased them.
- miR-155 was found to target SIRT1, and SIRT1 overexpression reversed miR-155's effects on IL-9 and Th9 cells.
Conclusions:
- miR-155 plays a crucial role in regulating Th9 cell differentiation in children with MRSA pneumonia.
- The mechanism involves miR-155 targeting SIRT1, impacting IL-9 production and Th9 cell numbers.
Abstract:
Th9 is a subset of CD4+ T cells that mainly secrete IL-9. Th9/IL-9 participates in immune response during Staphylococcus aureus and methicillin-resistant Staphylococcus aureus pneumonia (MRSA) infection. Here, we collected bronchoalveolar lavage fluid (BALF) from 30 children with MRSA pneumonia (MRSA group) and 10 children with bronchial foreign bodies (Control group). RT-PCR, ELISA and flow cytometry were used to detect the expression of miR-155 and IL-9 in BALF and the number of Th9 cells. CD4+ T cells isolated from BALF of MRSA and Control group were transfected with miR-155 mimic or inhibitor, and then induced Th9 cell differentiation. The results showed that the expression of miR-155 and IL-9 were significantly increased in BALF and Th9 cell of MRSA group, as well as the number of Th9 cells. miR-155 mimic upregulated IL-9 mRNA expression, IL-9 secretion and increased number of Th9 cells. On the contrary, miR-155 inhibitor inhibited IL-9 mRNA expression, IL-9 secretion and decreased number of Th9 cells. The dual luciferase assays demonstrated miR-155 can target binding to SIRT1 3'UTR. Moreover, overexpression of SIRT1 could reverse the effect of miR-155 mimic on IL-9 expression level, Th9 cell number and transcription factors PU.1 and IRF4 expression. In conclusion, miR-155 regulates Th9 differentiation in children with MRSA by targeting SIRT1.

