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Updated: May 17, 2025
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Published on: June 2, 2011
CD300ld promotes neutrophil bacterial phagocytosis in sepsis
Yuichi Akama1, Atsushi Murao1, Monowar Aziz1,2
1Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY 11030, United States.
Abstract:
Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. Neutrophils act as first line of defense against infection, but their function can become impaired in sepsis. CD300 antigen-like family member d (CD300ld), predominantly expressed on neutrophils, associates with Fc receptor common gamma-chain (FcRγ chain), a component vital for phagocytosis. In this study, we investigated the role of CD300ld in neutrophil phagocytosis. Our results demonstrate a marked decrease in CD300ld expression on neutrophils isolated from both septic mice and patients. CD300ld was positively correlated with bacterial phagocytosis in neutrophils. The transcriptomic analysis of CD300ld knock-out neutrophils revealed a downregulation of genes related to defense response to bacteria, suggesting that CD300ld is a key modulator of bacterial clearance. Stimulation of CD300ld with an agonist antibody in neutrophils led to the activation of Rac2, a key regulator of actin polymerization, facilitating the enhanced phagocytosis. Furthermore, CD300ld activation significantly enhanced the in vitro phagocytosis of Escherichia coli and Staphylococcus aureus by neutrophils. Septic mice adoptively transferred with CD300ld-activated neutrophils exhibited markedly reduced bacterial loads in the blood and peritoneum, decreased inflammatory cytokine levels, and alleviated organ injury. These findings highlight the critical role of CD300ld signaling in neutrophil-mediated bacterial clearance in sepsis and provide a solid foundation for future research aimed at developing novel immunotherapies against this deadly disease condition.
Insights
CD300 antigen-like family member d (CD300ld) on neutrophils is crucial for fighting sepsis. Activating CD300ld enhances bacterial clearance, reducing sepsis severity and organ damage in mice.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Sepsis involves a dangerous immune response to infection, impairing neutrophil function.
- CD300 antigen-like family member d (CD300ld) on neutrophils is linked to phagocytosis via the Fc receptor common gamma-chain (FcRγ chain).
Purpose of the Study:
- To investigate the role of CD300ld in neutrophil phagocytosis and its impact on sepsis.
- To explore CD300ld as a potential therapeutic target for sepsis.
Main Methods:
- Measured CD300ld expression in neutrophils from septic mice and patients.
- Performed transcriptomic analysis of CD300ld knock-out neutrophils.
- Stimulated neutrophils with CD300ld agonist antibodies.
- Assessed bacterial phagocytosis in vitro and in vivo.
- Evaluated sepsis outcomes in mice receiving CD300ld-activated neutrophils.
Main Results:
- CD300ld expression decreased in neutrophils during sepsis.
- CD300ld expression positively correlated with bacterial phagocytosis.
- CD300ld deficiency impaired bacterial defense gene expression.
- CD300ld activation enhanced neutrophil phagocytosis of E. coli and S. aureus.
- Adoptive transfer of CD300ld-activated neutrophils reduced bacterial load, inflammation, and organ injury in septic mice.
Conclusions:
- CD300ld is a critical regulator of neutrophil phagocytosis and bacterial clearance in sepsis.
- CD300ld signaling represents a promising target for novel sepsis immunotherapies.
