BTLA expression contributes to septic morbidity and mortality by inducing innate inflammatory cell dysfunction.

Area of Science:

• Immunology
• Sepsis Pathophysiology
• Innate Immune Response

Background:

• Sepsis involves systemic inflammation, making a proper innate immune response critical for prevention.
• B- and T-lymphocyte attenuator (BTLA) is an immune-regulatory receptor found on both adaptive and innate immune cells.
• BTLA's role in sepsis and its impact on pathogen clearance remain unclear.

Purpose of the Study:

• To investigate the role of BTLA in experimental sepsis.
• To elucidate the mechanisms by which BTLA influences pathogen clearance and immune cell activation during sepsis.
• To assess the potential of BTLA and its ligand HVEM as diagnostic markers and therapeutic targets for sepsis.

Main Methods:

• Acute experimental sepsis was induced in mice using the cecal ligation and puncture (CLP) model.
• Flow cytometry was used to analyze immune cell populations (macrophages, monocytes, DCs, neutrophils) in the peritoneum and blood.
• Bacterial burden, IL-10 levels, and survival rates were assessed in wild-type (WT) and BTLA knockout (BTLA-/-) mice post-CLP.

Main Results:

• Sepsis induction led to increased infiltration of BTLA- and HVEM-expressing immune cells in the mouse peritoneum.
• BTLA-/- mice showed enhanced activation of peritoneal immune cells, reduced bacterial burden, and lower IL-10 induction compared to WT mice.
• BTLA-/- mice exhibited significantly improved survival rates and reduced organ injury following sepsis induction.
• Elevated BTLA+ and HVEM+ monocytes and HVEM+ granulocytes were observed in septic ICU patients.

Conclusions:

• BTLA plays a critical inhibitory role in the innate immune response during sepsis.
• Targeting BTLA or HVEM may offer a novel therapeutic strategy for sepsis treatment.
• BTLA and HVEM show potential as diagnostic biomarkers for assessing the innate immune status in sepsis patients.