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.