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Theranostics 2024; 14(6):2589-2604. doi:10.7150/thno.93812 This issue Cite

Research Paper

Siglec-F+ neutrophils in the spleen induce immunosuppression following acute infection

Chaoxiong Liao1,*, Shuhua Luo1,*, Xiaolei Liu1,2, Lina Zhang1,2, Pengyun Xie1, Wending Zhou1,2, Yue Lu1,2, Hanhui Zhong1, Xuedi Zhang1,2, Ziying Xiong1,2, Xiao Huang1,2, Guixi Mo1✉, Daqing Ma3,4✉, Jing Tang1,#,✉

1. Department of Anesthesiology, Affiliated hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong, China.
2. Guangdong Medical University, Zhanjiang 524000, Guangdong, China.
3. Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
4. Children's hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
*These authors contributed equally.
#Lead contact.

✉ Corresponding authors: tanglitangjingcom (J.T.), d.maac.uk (D.Q.M.), mogxicom (G.X.M.).

Citation:
Liao C, Luo S, Liu X, Zhang L, Xie P, Zhou W, Lu Y, Zhong H, Zhang X, Xiong Z, Huang X, Mo G, Ma D, Tang J. Siglec-F+ neutrophils in the spleen induce immunosuppression following acute infection. Theranostics 2024; 14(6):2589-2604. doi:10.7150/thno.93812. https://www.thno.org/v14p2589.htm
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Abstract

Graphic abstract

Background: The mechanisms underlying the increased mortality of secondary infections during the immunosuppressive phase of sepsis remain elusive.

Objectives: We sought to investigate the role of Siglec-F+ neutrophils on splenic T lymphocytes in the immunosuppressed phase of sepsis and on secondary infection in PICS mice, and to elucidate the underlying mechanisms.

Methods: We established a mouse model of sepsis-induced immunosuppression followed by secondary infection with LPS or E. coli. The main manifestation of immunosuppression is the functional exhaustion of splenic T lymphocytes. Treg depletion reagent Anti-IL-2, IL-10 blocker Anti-IL-10R, macrophage depletion reagent Liposomes, neutrophil depletion reagent Anti-Ly6G, neutrophil migration inhibitor SB225002, Siglec-F depletion reagent Anti-Siglec-F are all used on PICS mice. The function of neutrophil subsets was investigated by adoptive transplantation and the experiments in vitro.

Results: Compared to other organs, we observed a significant reduction in pro-inflammatory cytokines in the spleen, accompanied by a marked increase in IL-10 production, primarily by infiltrating neutrophils. These infiltrating neutrophils in the spleen during the immunosuppressive phase of sepsis undergo phenotypic change in the local microenvironment, exhibiting high expression of neutrophil biomarkers such as Siglec-F, Ly6G, and Siglec-E. Depletion of neutrophils or specifically targeting Siglec-F leads to enhance the function of T lymphocytes and a notable improvement in the survival of mice with secondary infections.

Conclusions: We identified Siglec-F+ neutrophils as the primary producers of IL-10, which significantly contributed to T lymphocyte suppression represents a novel finding with potential therapeutic implications.

Keywords: Sepsis, Immunosuppression, Secondary challenge, Siglec-F, Neutrophils, T lymphocytes, IL-10

Citation styles

APA
Liao, C., Luo, S., Liu, X., Zhang, L., Xie, P., Zhou, W., Lu, Y., Zhong, H., Zhang, X., Xiong, Z., Huang, X., Mo, G., Ma, D., Tang, J. (2024). Siglec-F+ neutrophils in the spleen induce immunosuppression following acute infection. Theranostics, 14(6), 2589-2604. https://doi.org/10.7150/thno.93812.

ACS
Liao, C.; Luo, S.; Liu, X.; Zhang, L.; Xie, P.; Zhou, W.; Lu, Y.; Zhong, H.; Zhang, X.; Xiong, Z.; Huang, X.; Mo, G.; Ma, D.; Tang, J. Siglec-F+ neutrophils in the spleen induce immunosuppression following acute infection. Theranostics 2024, 14 (6), 2589-2604. DOI: 10.7150/thno.93812.

NLM
Liao C, Luo S, Liu X, Zhang L, Xie P, Zhou W, Lu Y, Zhong H, Zhang X, Xiong Z, Huang X, Mo G, Ma D, Tang J. Siglec-F+ neutrophils in the spleen induce immunosuppression following acute infection. Theranostics 2024; 14(6):2589-2604. doi:10.7150/thno.93812. https://www.thno.org/v14p2589.htm

CSE
Liao C, Luo S, Liu X, Zhang L, Xie P, Zhou W, Lu Y, Zhong H, Zhang X, Xiong Z, Huang X, Mo G, Ma D, Tang J. 2024. Siglec-F+ neutrophils in the spleen induce immunosuppression following acute infection. Theranostics. 14(6):2589-2604.

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