Septic Macrophages Induce T Cells Immunosuppression in a Cell-cell Contact Manner with the Involvement of CR3

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Jan 8

PMID 38187232

Authors

Shunwei Huang

Ying Chen

Fangchen Gong

Weiwei Chen

Yanjun Zheng

Bing Zhao

Wen Shi

Zhitao Yang

Hongping Qu

Enqiang Mao

Erzhen Chen

Affiliations

Soon will be listed here.

Abstract

Background: In addition to excessive inflammation, immunosuppression has been recognized as a contributing factor to poor prognosis of sepsis. Although it has been reported that T cells can become functionally impaired during sepsis, the underlying mechanisms responsible for this phenomenon remain unclear. This study aims to elucidate the mechanisms by which macrophages induce immunosuppression in T cells.

Methods: In an in vivo setting, C57BL-6J mice were subjected to cecal ligation and puncture (CLP) with or without depletion of macrophages, and the functions of T cells were assessed. In vitro experiments involved direct co-culture or separate culture of T cells and septic macrophages using a transwell system, followed by analysis of T cell immunity. Additionally, a siRNA targeting CD18 on macrophages was utilized to investigate the role of complement receptor 3 (CR3).

Results: Both macrophages and T cells exhibited immunosuppression during sepsis. In the in vivo experiments, the absence of macrophages partially alleviated T cell immunosuppression, as evidenced by restored vitality, increased production of TNF-α and IFN-γ, elevated CD8 T cell levels, and decreased CD25 T cell levels. In the in vitro experiments, direct co-culture of T cells with septic macrophages resulted in diminished T cell immunity, which was improved when T cells and macrophages were separated by a chamber wall. The expression of CR3 (CD11b/CD18) was upregulated on septic macrophages, and silencing of CD18 led to decreased TNF-α production by T cells, reduced CD4 T cell numbers, and increased CD25 T cell numbers.

Conclusion: In sepsis, macrophages induce immunosuppression in T cells through direct cell-cell contact, with the involvement of CR3.

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