Profound and persistent decrease of circulating dendritic cells is associated with ICU-acquired infection in patients with septic shock

Abstract

Septic shock induces a decrease in dendritic cells (DCs) that may contribute to sepsis-induced immunosuppression. We analyzed the time course of circulating DCs in patients with septic shock and its relation to susceptibility to intensive care unit (ICU)-acquired infections. We enrolled adult patients with septic shock (n = 43), non-septic shock (n = 29), and with sepsis without organ dysfunction (n = 16). Healthy controls (n = 16) served as reference. Blood samples were drawn on the day of shock (day 1), then after 3 and 7 days. Myeloid (mDC) and plasmacytoid (pDC) DCs were counted by flow cytometry. Cell surface HLA-DR expression was analyzed in both DC subsets. At day 1, median mDC and pDC counts were dramatically lower in septic shock patients as compared to healthy controls (respectively, 835 mDCs and 178 pDCs/ml vs. 19,342 mDCs and 6,169 pDCs/ml; P < 0.0001) but also to non-septic shock and sepsis patients (P < 0.0001). HLA-DR expression was decreased in both mDCs and pDCS within the septic shock group as compared to healthy controls. DC depletion was sustained for at least 7 days in septic shock patients. Among them, 10/43 developed ICU-acquired infections after a median of 9 [7.5-11] days. At day 7, mDC counts increased in patients devoid of secondary infections, whereas they remained low in those who subsequently developed ICU-acquired infections. Septic shock is associated with profound and sustained depletion of circulating DCs. The persistence of low mDC counts is associated with the development of ICU-acquired infections, suggesting that DC depletion is a functional feature of sepsis-induced immunosuppression.