Polymorphonuclear Cells Show Features of Dysfunctional Activation During Fatal Sepsis

Authors

HORTOVA-KOHOUTKOVA Marcela ZUANI DE Marco LÁZNIČKOVÁ Petra BENDICKOVA Kamila MRKVA Ondřej ANDREJČINOVÁ Ivana MÝTNIKOVÁ Alexandra POLANSKY Ondrej KOCI Kamila TOMÁŠKOVÁ Veronika ŠRÁMEK Vladimír HELÁN Martin FRIČ Jan

Year of publication 2021
Type Article in Periodical
Magazine / Source Frontiers in Immunology
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.frontiersin.org/articles/10.3389/fimmu.2021.741484/full
Doi http://dx.doi.org/10.3389/fimmu.2021.741484
Keywords sepsis; polymorphonuclears; septic shock; transcriptomics; proteomics; dysfunctionality
Description Sepsis and septic shock remain leading causes of morbidity and mortality for patients in the intensive care unit. During the early phase, immune cells produce various cytokines leading to prompt activation of the immune system. Polymorphonuclear leukocytes (PMNs) respond to different signals producing inflammatory factors and executing their antimicrobial mechanisms, resulting in the engulfment and elimination of invading pathogens. However, excessive activation caused by various inflammatory signals produced during sepsis progression can lead to the alteration of PMN signaling and subsequent defects in their functionality. Here, we analyzed samples from 34 patients in septic shock, focusing on PMNs gene expression and proteome changes associated with septic shock. We revealed that, compared to those patients who survived longer than five days, PMNs from patients who had fulminant sepsis were characterized by a dysfunctional hyper-activation, show altered metabolism, and recent exit from the cell cycle and signs of cellular lifespan. We believe that this multi-omics approach, although limited, pinpoints the alterations in PMNs' functionality, which may be rescued by targeted treatments.
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