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IL-9 promotes methicillin-resistant Staphylococcus aureus pneumonia by regulating the polarization and phagocytosis of macrophages
ABSTRACT In this study, we examined the effect of Il9 deletion on macrophages in methicillin-resistant Staphylococcus aureus (MRSA) infection. MRSA-infected mice were employed for the in vivo experiments, and RAW264.7 cells were stimulated with MRSA for the in vitro experiments. Macrophage polarizat...
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Published in: | Infection and immunity 2023-10, Vol.91 (10), p.e0016623-e0016623 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | ABSTRACT
In this study, we examined the effect of
Il9
deletion on macrophages in methicillin-resistant
Staphylococcus aureus
(MRSA) infection. MRSA-infected mice were employed for the
in vivo
experiments, and RAW264.7 cells were stimulated with MRSA for the
in vitro
experiments. Macrophage polarization was determined by flow cytometry and quantitative real-time PCR; macrophage phagocytosis was assessed by flow cytometry and laser scanning confocal microscopy; cell apoptosis was assessed by flow cytometry and western blotting.
Il9
deletion markedly elevated macrophage phagocytosis and M2 macrophages in MRSA infection, which was accompanied by elevated expression of
Il10
and
Arg1
and reduced expression of
Inos
, tumor necrosis factor-α (
Tnfα)
, and
Il6. Il9
deletion also inhibited macrophage apoptosis in MRSA infection, which was manifested by elevated B-cell lymphoma 2 (BCL-2) protein level and reduced protein levels of cleaved cysteine protease 3 (CASPASE-3) and BCL2-Associated X (BAX). Both the
in vivo
and
in vitro
experiments further showed the activation of phosphoinositide 3-kinase (PI3K)/AKT (also known as protein kinase B, PKB) signaling pathway in MRSA infection and that the regulation of
Il9
expression may be dependent on Toll-like receptor (TLR) 2/PI3K pathway. The above results showed that
Il9
deletion exhibited a protective role against MRSA infection by promoting M2 polarization and phagocytosis of macrophages and the regulation of
Il9
partly owing to the activation of TLR2/PI3K pathway, proposing a novel therapeutic strategy for MRSA-infected pneumonia. |
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ISSN: | 0019-9567 1098-5522 |
DOI: | 10.1128/iai.00166-23 |