Circulating myeloid and plasmacytoid dendritic cells are strongly diminished in septic shock

Background

Dendritic cells (DCs) play a key role in the initiation and integration of innate and adaptive immune responses to microbial infection. In contrast to neutrophils, macrophages or lymphocytes, there are virtually no data on the time course of circulating DCs in septic shock. Using a novel specific and sensitive assay, we analyzed the evolution of circulating myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in septic shock.

Methods

We enrolled immunocompetent adult patients with septic shock (SS, n = 43) and with shock from other etiologies (NSS, n = 29). Sixteen healthy controls (HC) were also used as reference for mDCs and pDCs. Blood samples (200 μl) were drawn on the day of shock, then after 3 and 7 days. DC analyses were performed using the DC-labelling kit Trucount^® assay (BD Biosciences, San Jose, CA, USA). CD11c⁺CD123^- cells (mDCs) and CD11c^-CD123⁺ cells (pDCs) were selected and counted by flow cytometry (FACSCanto™; BD Biosciences). The HLA-DR mean fluorescence index was measured.

Results

The age, sex ratio, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment score, nosocomial infection (NI) and mortality rates did not statistically differ between SS and NSS patients. On day 1, mDC and pDC counts were significantly lower in both SS and NSS patients as compared with controls (P < 0.001). Patients with SS had significantly lower mDC and pDC counts than NSS patients (P < 0.001) both at day 1 and day 3. The HLA-DR mean fluorescence index of mDCs and pDCs was lower in SS patients compared with HC (P = 0.005 and P = 0.037, respectively) but did not differ between other groups. Interestingly, 10 out of the 43 SS patients developed NI after a median time of 9 (7.5 to 11) days in the ICU. Whereas mDCs increased in patients without NI, mDC counts remained low at day 7 in patients who developed NI: mDC counts and their relative variation between day 1 and day 7 were significantly lower in patients who developed NI than in those who did not (P < 0.05). Logistic regression analysis indicates that a negative mDC relative variation is associated with an increased risk of nosocomial infection with an odds ratio of 22 (2.53 to 191) (P = 0.005).

Conclusion

Circulating mDC and pDC counts are lower in SS than in NSS as early as day 1. The persistence of a low count of mDCs after SS seems to be associated with the advent of nosocomial infection during the ICU stay.