Sepsis is a syndrome with hyperactivity of TH17-like innate immunity and hypoactivity of adaptive immunity

TL;DR

This study reveals that sepsis involves simultaneous hyperactivity of innate immunity, especially TH17-like responses, and hypoactivity of adaptive immunity, highlighting complex immune dysregulation.

Contribution

It provides a comprehensive gene expression profile showing innate immune activation and adaptive immune suppression in sepsis patients, integrating both hyperimmune and hypoimmune theories.

Findings

Innate immunity genes are significantly up-regulated.

Adaptive immunity genes are predominantly down-regulated.

Treg-related genes are up-regulated.

Abstract

Currently, there are two major theories for the pathogenesis of sepsis: hyperimmune and hypoimmune. Hyperimmune theory suggests that cytokine storm causes the symptoms of sepsis. On the contrary, hypoimmune theory suggests that immunosuppression causes the manifestations of sepsis. By using microarray study, this study implies that hyperactivity of TH17-like innate immunity and failure of adaptive immunity are noted in sepsis patients. I find out that innate immunity related genes are significantly up-regulated including CD14, TLR1,2,4,5,8, HSP70, CEBP proteins, AP1(JUNB, FOSL2), TGF-{\beta}, IL-6, TGF-{\alpha}, CSF2 receptor, TNFRSF1A, S100A binding proteins, CCR2, formyl peptide receptor2, amyloid proteins, pentraxin, defensins, CLEC5A, whole complement machinery, CPD, NCF, MMP, neutrophil elastase, caspases, IgG and IgA Fc receptors(CD64, CD32), ALOX5, PTGS, LTB4R, LTA4H, and ICAM1. Majority of adaptive immunity genes are down-regulated including MHC related genes, TCR genes, granzymes/perforin, CD40, CD8, CD3, TCR signaling, BCR signaling, T & B cell specific transcription factors, NK killer receptors, and TH17 helper specific transcription factors(STAT3, RORA, REL). In addition, Treg related genes are up-regulated including TGF{\beta}, IL-15, STAT5B, SMAD2/4, CD36, and thrombospondin. Thus, both hyperimmune and hypoimmune play important roles in the pathophysiology of sepsis.