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

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	102339
Journal	iScience
Volume	24
Issue number	4
DOIs	https://doi.org/10.1016/j.isci.2021.102339
Publication status	Published - 2021 Apr 23

Bibliographical note

Funding Information:
We thank Berit Olofsson for excellent technical assistance with isolation of CD14+ monocytes. We thank Dr. Oonagh Shannon and Frida Palm for access to and excellent technical assistant with the flow cytometer. We thank Tilde Andersson and Dr. Gizem Ert?rk-Bergdahl for excellent technical assistance with the Biacore/SPR experiments. This study was funded by grants from Knut and Alice Wallenberg Foundation, Alfred ?sterlund Foundation, Hansa Biopharma, the Swedish Government Funds for Clinical Research (ALF), Royal Physiographic Society of Lund and the Swedish Research Council (project 7480). Conceptualization: A.N. I.-M.F. and L.B. Methodology: A.N. and W.B. Validation: A.N. I.-M.F. and L.B. Formal analysis: A.N. L.H. and C.K. Investigation: A.N. L.H. C.K. and I.-M.F. Data curation: L.H. and C.K. Writing ? Original draft: A.N. I.-M.F. and L.B. Writing ? Review & Editing: A.N. L.H. C.K. W.B. I.-M.F. and L.B. Visualization: A.N. Supervision: A.N. and L.B. Project administration: A.N. and L.B. Funding acquisition: A.N. I.-M.F. and L.B. The authors declare no competing interest.

Publisher Copyright:
© 2021 The Authors

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Subject classification (UKÄ)

Infectious Medicine
Microbiology in the medical area

Free keywords

Clinical Microbiology
Immunology
Microbiology

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10.1016/j.isci.2021.102339Licence: CC BY

Cite this

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title = "Streptococcal protein SIC activates monocytes and induces inflammation",

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",

author = "Ariane Neumann and Lotta Happonen and Christofer Karlsson and Wael Bahnan and Frick, {Inga Maria} and Lars Bj{\"o}rck",

note = "Funding Information: We thank Berit Olofsson for excellent technical assistance with isolation of CD14+ monocytes. We thank Dr. Oonagh Shannon and Frida Palm for access to and excellent technical assistant with the flow cytometer. We thank Tilde Andersson and Dr. Gizem Ert?rk-Bergdahl for excellent technical assistance with the Biacore/SPR experiments. This study was funded by grants from Knut and Alice Wallenberg Foundation, Alfred ?sterlund Foundation, Hansa Biopharma, the Swedish Government Funds for Clinical Research (ALF), Royal Physiographic Society of Lund and the Swedish Research Council (project 7480). Conceptualization: A.N. I.-M.F. and L.B. Methodology: A.N. and W.B. Validation: A.N. I.-M.F. and L.B. Formal analysis: A.N. L.H. and C.K. Investigation: A.N. L.H. C.K. and I.-M.F. Data curation: L.H. and C.K. Writing ? Original draft: A.N. I.-M.F. and L.B. Writing ? Review & Editing: A.N. L.H. C.K. W.B. I.-M.F. and L.B. Visualization: A.N. Supervision: A.N. and L.B. Project administration: A.N. and L.B. Funding acquisition: A.N. I.-M.F. and L.B. The authors declare no competing interest. Publisher Copyright: {\textcopyright} 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

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doi = "10.1016/j.isci.2021.102339",

language = "English",

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T1 - Streptococcal protein SIC activates monocytes and induces inflammation

AU - Neumann, Ariane

AU - Happonen, Lotta

AU - Karlsson, Christofer

AU - Bahnan, Wael

AU - Frick, Inga Maria

AU - Björck, Lars

N1 - Funding Information: We thank Berit Olofsson for excellent technical assistance with isolation of CD14+ monocytes. We thank Dr. Oonagh Shannon and Frida Palm for access to and excellent technical assistant with the flow cytometer. We thank Tilde Andersson and Dr. Gizem Ert?rk-Bergdahl for excellent technical assistance with the Biacore/SPR experiments. This study was funded by grants from Knut and Alice Wallenberg Foundation, Alfred ?sterlund Foundation, Hansa Biopharma, the Swedish Government Funds for Clinical Research (ALF), Royal Physiographic Society of Lund and the Swedish Research Council (project 7480). Conceptualization: A.N. I.-M.F. and L.B. Methodology: A.N. and W.B. Validation: A.N. I.-M.F. and L.B. Formal analysis: A.N. L.H. and C.K. Investigation: A.N. L.H. C.K. and I.-M.F. Data curation: L.H. and C.K. Writing ? Original draft: A.N. I.-M.F. and L.B. Writing ? Review & Editing: A.N. L.H. C.K. W.B. I.-M.F. and L.B. Visualization: A.N. Supervision: A.N. and L.B. Project administration: A.N. and L.B. Funding acquisition: A.N. I.-M.F. and L.B. The authors declare no competing interest. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4/23

Y1 - 2021/4/23

N2 - 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.

AB - 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.

KW - Clinical Microbiology

KW - Immunology

KW - Microbiology

U2 - 10.1016/j.isci.2021.102339

DO - 10.1016/j.isci.2021.102339

M3 - Article

C2 - 33855284

AN - SCOPUS:85103704746

SN - 2589-0042

VL - 24

JO - iScience

JF - iScience

IS - 4

M1 - 102339

ER -

Streptococcal protein SIC activates monocytes and induces inflammation

Abstract

Bibliographical note

Subject classification (UKÄ)

Free keywords

Access to Document

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Cite this