Function is Dissociated From Activation-Related Immunophenotype on Phagocytes From Patients With SIRS/Sepsis Syndrome

Abstract

Sepsis is a life-threatening condition associated with failure of at least one organ in the presence of infection. Along with SIRS, the acute systemic inflammatory syndrome without documented infection, sepsis represents a main health problem in intensive care units around the world. Hypercytokinemia and overexpression of activation-markers on leukocytes are frequently reported in SIRS/sepsis. Leukocyte functions including antibody mediated-phagocytosis, pathogen recognition, and migration appear to be disabled in SIRS/septic patients. Our aim was to evaluate the so-called activation immunophenotype and functions related to infection contention in phagocytes from patients with sepsis. We analyzed blood samples from 44 patients with SIRS/sepsis and 14 healthy volunteers. CD16, CD69, CD64, CCR7, and TREM-1 levels were determined on the surface of neutrophils and monocytes. Phagosome maturation and p38, STAT3, and STAT5 phosphorylation were evaluated in these phagocytes. As expected, sepsis and SIRS patients had increased serological levels of pro- and anti-inflammatory cytokines. E coli internalization was not increased in monocytes from patients with SIRS/sepsis, despite increased numbers of circulating neutrophils and monocytes (P < 0.05) and overexpression of CD64 and CD69 in neutrophils (P < 0.05), TREM-1 (P < 0.01), CD69 (P < 0.001), and CCR7 (P < 0.05). Moreover, phagosome maturation was decreased in phagocytes from patients with SIRS/sepsis syndrome (P < 0.00001). Furthermore, p38 and STAT-3 phosphorylation elicited by LPS or IL-10 (respectively) was diminished in neutrophils and monocytes from patients (P < 0.05). Our results indicate that “activation markers” may not reflect higher functionality, so a more profound analysis should be made before assuming that the activated immunophenotype means increased phagocyte responses.

Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis

“…Contrary to other reports [17,18], the total numbers of circulating monocytes remain unchanged in our study between septic (n = 36) and non-septic (n = 40) ICU patients (Figure 2A, right panel). However, we could observe alterations in the composition of monocyte populations dependent on the presence of sepsis.…”

“…Several studies reported increased numbers of circulating monocytes in patients with diagnosed sepsis [17,18], including alterations of the monocyte subset distribution [22]. We herein investigated the abundance and phenotype of different monocyte subpopulations in a prospective patient study, including 54 healthy controls (HC), 42 standard care patients (SC) with confirmed infection, and 76 critically ill patients upon admission to the intensive care unit (ICU) ( Table 1).…”

“…Concerning innate immunity, several reports demonstrate that the numbers of circulating monocytes are increased in patients with diagnosed sepsis [17][18][19]. In humans, monocytes are subdivided into at least three different populations according to their surface expression of the LPS-co-receptor CD14 and the Fcγ receptor CD16.…”

Phagocytosis–Inflammation Crosstalk in Sepsis: New Avenues for Therapeutic Intervention

“…Many other life-threatening, noninfectious causes such as shock states, trauma or ischemia–reperfusion injury are associated with systemic inflammatory response syndrome (SIRS) ( 78 ). Although the etiology of these pathologies is different, human SIRS and sepsis share similar patterns of cytokine expression ( 79 ). Like in sepsis, this robust inflammatory storm is also associated with the extensive formation of cell debris arising from apoptosis ( 80 ) and necroptosis ( 81 ) of many different cell types, which needs to be cleared by phagocytes.…”

Fc-gamma receptor expression and cytokine response to intravenous human immunoglobulin in mothers and neonates

“…CD16 and CD32 on monocytes are less expressed on adults than in neonates, and the CD64 expression on granulocytes is higher in neonates than adults (15). Also, it has been reported that after IVIg treatment, the FcγR expression changes on effector cells in mice (16,17).…”