PMID- 32702113 OWN - NLM STAT- MEDLINE DCOM- 20220201 LR - 20220201 IS - 1537-6613 (Electronic) IS - 0022-1899 (Linking) VI - 223 IP - 5 DP - 2021 Mar 3 TI - Signaling Lymphocytic Activation Molecule Family-7 Alleviates Corneal Inflammation by Promoting M2 Polarization. PG - 854-865 LID - 10.1093/infdis/jiaa445 [doi] AB - 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-gamma 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. CI - (c) The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. FAU - Zhu, Siying AU - Zhu S AD - Program of Infection and Immunology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China. AD - Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China. FAU - Chen, Yu AU - Chen Y AD - Program of Infection and Immunology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China. AD - Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China. FAU - Lao, Juanfeng AU - Lao J AD - Program of Infection and Immunology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China. AD - Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China. FAU - Wu, Chenglin AU - Wu C AD - Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Zhan, Xiaoxia AU - Zhan X AD - Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Wu, Yongjian AU - Wu Y AD - Program of Infection and Immunology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China. AD - Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China. FAU - Shang, Yuqi AU - Shang Y AD - Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China. FAU - Zou, Zhengyu AU - Zou Z AD - Program of Infection and Immunology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China. AD - Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China. FAU - Zhou, Jinyu AU - Zhou J AD - Program of Infection and Immunology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China. AD - Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China. FAU - Ji, Xiang AU - Ji X AD - Program of Infection and Immunology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China. AD - Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China. FAU - Huang, Xi AU - Huang X AD - Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China. FAU - Shi, Xiaomin AU - Shi X AD - Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Wu, Minhao AU - Wu M AD - Program of Infection and Immunology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China. AD - Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China. AD - Guangdong Engineering and Technology Research Center for Disease-Model Animals, Sun Yat-sen University, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Signaling Lymphocytic Activation Molecule Family) RN - 0 (Slamf7 protein, mouse) SB - IM MH - Animals MH - Cell Polarity MH - *Cornea/physiopathology MH - Disease Progression MH - *Inflammation MH - *Keratitis/drug therapy/microbiology MH - Macrophages/*cytology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Pseudomonas Infections MH - Pseudomonas aeruginosa MH - Signal Transduction MH - Signaling Lymphocytic Activation Molecule Family/*genetics OTO - NOTNLM OT - SLAMF7 OT - M1/M2 polarization OT - corneal inflammation EDAT- 2020/07/24 06:00 MHDA- 2022/02/02 06:00 CRDT- 2020/07/24 06:00 PHST- 2020/04/30 00:00 [received] PHST- 2020/07/11 00:00 [revised] PHST- 2020/07/17 00:00 [accepted] PHST- 2020/07/24 06:00 [pubmed] PHST- 2022/02/02 06:00 [medline] PHST- 2020/07/24 06:00 [entrez] AID - 5875656 [pii] AID - 10.1093/infdis/jiaa445 [doi] PST - ppublish SO - J Infect Dis. 2021 Mar 3;223(5):854-865. doi: 10.1093/infdis/jiaa445.