Signaling lymphocytic activation molecule family-7 alleviates corneal inflammation by promoting M2 polarization
S Zhu, Y Chen, J Lao, C Wu, X Zhan… - The Journal of …, 2021 - academic.oup.com
S Zhu, Y Chen, J Lao, C Wu, X Zhan, Y Wu, Y Shang, Z Zou, J Zhou, X Ji, X Huang, X Shi…
The Journal of infectious diseases, 2021•academic.oup.comBackground Signaling lymphocytic activation molecule family-7 (SLAMF7) functions as an
immune checkpoint molecule on macrophages in antitumor immunity. However, its role in
bacterial infection remains largely unknown. Methods Bone marrow-derived macrophages
(BMDMs) isolated from wild-type (WT) or SLAMF7 knockout (KO) mice were infected with
bacteria or treated with lipopolysaccharide/interferon-γ to investigate the expression and
function of SLAMF7 in macrophage polarization. A Pseudomonas aeruginosa keratitis …
immune checkpoint molecule on macrophages in antitumor immunity. However, its role in
bacterial infection remains largely unknown. Methods Bone marrow-derived macrophages
(BMDMs) isolated from wild-type (WT) or SLAMF7 knockout (KO) mice were infected with
bacteria or treated with lipopolysaccharide/interferon-γ to investigate the expression and
function of SLAMF7 in macrophage polarization. A Pseudomonas aeruginosa keratitis …
Background
Signaling lymphocytic activation molecule family-7 (SLAMF7) functions as an immune checkpoint molecule on macrophages in antitumor immunity. However, its role in bacterial infection remains largely unknown.
Methods
Bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) or SLAMF7 knockout (KO) mice were infected with bacteria or treated with lipopolysaccharide/interferon-γ to investigate the expression and function of SLAMF7 in macrophage polarization. A Pseudomonas aeruginosa keratitis murine model was established to explore the effect of SLAMF7 on P. aeruginosa keratitis using WT vs SLAMF7 KO mice, or recombinant SLAMF7 vs phosphate-buffered saline-treated mice, respectively.
Results
SLAMF7 expression was enhanced on M1-polarized or bacterial-infected macrophages, and infiltrating macrophages in P. aeruginosa-infected mouse corneas. SLAMF7 promoted M2 polarization by inducing STAT6 activation. In vivo data showed that SLAMF7 KO aggravated, while treatment with recombinant SLAMF7 alleviated, corneal inflammation and disease severity. In addition, blockage of M2 polarization by Arg-1 inhibitor abrogated the effect of recombinant SLAMF7 in disease progression.
Conclusions
SLAMF7 expression in macrophages was induced upon M1 polarization or bacterial infection and alleviated corneal inflammation and disease progression of P. aeruginosa keratitis by promoting M2 polarization. These findings may provide a potential strategy for the treatment of P. aeruginosa keratitis.
Oxford University Press