Background:
Necrotizing soft tissue infections (NSTI) are severe, life-threatening invasive infections caused most often by Group A streptococcus (GAS). These infections have high mortality, amputations rates and risk of developing toxic shock syndrome1. In this project, we studied the local and systemic immune responses to identify key mechanisms driving NSTI pathogenesis.
Methods:
We analyzed biopsies and plasma samples from 46 NSTI patients from the INFECT biobank1 with monomicrobial GAS infections. Tissue biopsies were processed for RNA sequencing, while plasma samples were included in the Protein Blood Atlas (https://www.proteinatlas.org/humanproteome/blood) and measured using Olink® Explore (1463 proteins). As control groups, we included plasma samples from 19 cellulitis patients and 34 healthy individuals in the Olink measurements.
Results:
The transcriptome analysis suggested a heightened immune response including cytokine production, phagocytosis, and T and B cell activation; and downregulation of genes related to epidermis development and energy production in patients with less severe disease based on Sequential Organ Failure Assessment (SOFA) score or without septic shock. The comparison of the plasma proteomes indicated high immune activation including myeloid leukocyte activation and type 2 immune responses in NSTI, while cellulitis was associated with tissue and nerve development processes. Lastly, NSTI also showed an upregulated immune response activation in comparison to other infections included in the blood atlas.
Conclusions:
Our results highlight the differential immune responses at the local site and systemic level, providing valuable insights into NSTI pathogenesis. The relevant pathways represent potential targets of intervention and are of interest to explore in future studies.