Profound and Persistent Decrease of Circulating Dendritic Cells is Associated with ICU-acquired Infection in Patients with Septic Shock

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.