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

• DOI: 10.1189/jlb.1211641
• Publication Date: 2012-03-30T04:52:53Z
• Authors: Nicholas J Shubin; Chun S Chung; Daithi S Heffernan; Lydea R Irwin; Sean F Monaghan; Alfred Ayala
• Keywords: BTLA; Monocyte

Abstract BTLA expression contributes to increased septic morbidity, mortality, and decreased innate cell activity in mice, while BTLA+ blood monocyte levels increase ICU patients. A proper inflammatory response is essential for prevention of the systemic inflammation associated with sepsis. an immune-regulatory receptor demonstrated be expressed not only on adaptive immune populations have potent inhibitory effects CD4+ T cells but also (CD11c+ CD11b+ cells) has been shown diminish pathogen clearance following bacterial parasite infection. The role sepsis mechanisms by which alters clearance, however, addressed clearly. Here, we show that acute experimental induction mice (CLP), number infiltrating BTLA- HVEM (the ligand BTLA)-expressing macrophages, monocytes, mature immature DCs, neutrophils peritoneum compared sham surgery, suggesting a high level HVEM:BTLA interactions occurs between these at site insult. Given this, evaluated BTLA−/− 24 h post-CLP, observed marked degree activation populations, as well reduction peritoneal burden IL-10 induction, most importantly, exhibited higher rate survival protection from organ injury when WT mice. Such changes were restricted circulating HVEM+ monocytes granulocytes patients, supporting and/or potential, novel diagnostic markers response/status therapeutic targets