Marked alterations of neutrophil functions during sepsis-induced immunosuppression

Abstract

Severe septic syndromes deeply impair innate and adaptive immunity and are responsible for sepsis-induced immunosuppression. Although neutrophils represent the first line of defense against infection, little is known about their phenotype and functions a few days after sepsis, when the immunosuppressive phase is maximal (i.e., between d 3 and 8). The objective of the present study was to perform, for the first time, a global evaluation of neutrophil alterations in immunosuppressed septic patients (at d 3-4 and d 6-8) using phenotypic and functional studies. In addition, the potential association of these parameters and deleterious outcomes was assessed. Peripheral blood was collected from 43 septic shock patients and compared with that of 23 healthy controls. In the septic patients, our results highlight a markedly altered neutrophil chemotaxis (functional and chemokine receptor expressions), oxidative burst, and lactoferrin content and an increased number of circulating immature granulocytes (i.e., CD10(dim)CD16(dim)). These aspects were associated with an increased risk of death after septic shock. In contrast, phagocytosis and activation capacities were conserved. To conclude, circulating neutrophils present with phenotypic, functional, and morphologic alterations a few days after sepsis onset. These dysfunctions might participate in the deleterious role of sepsis-induced immunosuppression. The present results open new perspectives in the mechanisms favoring nosocomial infections after septic shock. They deserve to be further investigated in a larger clinical study and in animal models recapitulating these alterations.

Endotoxin promotes neutrophil hierarchical chemotaxis via the p38-membrane receptor pathway

“…Neutrophils are the first defensive line of immune cells against bacterial pathogen infection [3, 12, 13]. Neutrophils can eliminate pathogens by phagocytosis, degranulation and neutrophil extracellular traps (NETs) when recruited to the infectious foci [14–16].…”

Therapeutic targeting of neutrophil exocytosis

“…The localization of activated neutrophils within organs contributes to organ failure in sepsis. After 3–6 days patients develop an immunosuppressive state, including impaired neutrophil chemotaxis, reduced expression of plasma membrane receptors, impaired azurophilic and specific granule mobilization, and reduced oxidative burst …”

Expression of neutrophil surface markers in icteric neonates before and after phototherapy

“…The increase in CD10 activity reduces the concentration of these peptides and, consequently, the inflammatory process. Some studies on CD10 expression in infectious processes demonstrate a decline in CD10 expression in septic patients (23,24). In the study by Bae et al (2016), an increase in CD10 expression was observed in sepsis survival patients when compared with expression at diagnosis, while in nonsurvival patients CD10 expression remained low and stable.…”