Streptococcal protein SIC activates monocytes and induces inflammation

Ariane Neumann; Lotta Happonen; Christofer Karlsson; Wael Bahnan; Inga-Maria Frick; Lars Björck

doi:10.1016/j.isci.2021.102339

Streptococcal protein SIC activates monocytes and induces inflammation

iScience. 2021 Mar 20;24(4):102339. doi: 10.1016/j.isci.2021.102339. eCollection 2021 Apr 23.

Authors

Ariane Neumann¹, Lotta Happonen¹, Christofer Karlsson¹, Wael Bahnan¹, Inga-Maria Frick¹, Lars Björck¹

Affiliation

¹ Division of Infection Medicine, Department of Clinical Sciences, BMC, Lund University, 22184, Lund, Sweden.

Abstract

Streptococcus pyogenes is a major bacterial pathogen in the human population and isolates of the clinically important M1 serotype secrete protein Streptococcal inhibitor of complement (SIC) known to interfere with human innate immunity. Here we find that SIC from M1 bacteria interacts with TLR2 and CD14 on monocytes leading to the activation of the NF-κB and p38 MAPK pathways and the release of several pro-inflammatory cytokines (e.g. TNFα and INFγ). In human plasma, SIC binds clusterin and histidine-rich glycoprotein, and whole plasma, and these two purified plasma proteins enhanced the activation of monocytes by SIC. Isolates of the M55 serotype secrete an SIC homolog, but this protein did not activate monocytes. M1 isolates are common in cases of invasive S. pyogenes infections characterized by massive inflammation, and the results of this study indicate that the pro-inflammatory property of SIC contributes to the pathology of these severe clinical conditions.

Keywords: Clinical Microbiology; Immunology; Microbiology.