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Recognition of Lipoproteins by Toll-like Receptor 2 and DNA by the AIM2 Inflammasome Is Responsible for Production of Interleukin-1β by Virulent Suilysin-Negative Streptococcus suis Serotype 2

1
Research Group on Infectious Diseases in Production Animals & Swine and Poultry Infectious Diseases Research Centre, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, QC J2S 2M2, Canada
2
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M58 1A8, Canada
3
Division of Bioanalytical Chemistry, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, 23845 Borstel, Germany
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Pathogens 2020, 9(2), 147; https://doi.org/10.3390/pathogens9020147
Received: 31 January 2020 / Revised: 18 February 2020 / Accepted: 19 February 2020 / Published: 21 February 2020
Streptococcus suis serotype 2 is an important porcine bacterial pathogen and zoonotic agent causing sudden death, septic shock and meningitis. These pathologies are the consequence of an exacerbated inflammatory response composed of various mediators including interleukin (IL)-1β. Elevated levels of the toxin suilysin (SLY) were demonstrated to play a key role in S. suis-induced IL-1β production. However, 95% of serotype 2 strains isolated from diseased pigs in North America, many of which are virulent, do not produce SLY. In this study, we demonstrated that SLY-negative S. suis induces elevated levels of IL-1β in systemic organs, with dendritic cells contributing to this production. SLY-negative S. suis-induced IL-1β production requires MyD88 and TLR2 following recognition of lipoproteins. However, the higher internalization rate of the SLY-negative strain results in intracellularly located DNA being recognized by the AIM2 inflammasome, which promotes IL-1β production. Finally, the role of IL-1 in host survival during the S. suis systemic infection is beneficial and conserved, regardless of SLY production, via modulation of the inflammation required to control bacterial burden. In conclusion, this study demonstrates that SLY is not required for S. suis-induced IL-1β production. View Full-Text
Keywords: Streptococcus suis; interleukin-1; dendritic cell; suilysin-negative; Toll-like receptor 2; lipoprotein; AIM2 inflammasome; inflammation; septic shock Streptococcus suis; interleukin-1; dendritic cell; suilysin-negative; Toll-like receptor 2; lipoprotein; AIM2 inflammasome; inflammation; septic shock
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Lavagna, A.; Auger, J.-P.; Giradin, S.E.; Gisch, N.; Segura, M.; Gottschalk, M. Recognition of Lipoproteins by Toll-like Receptor 2 and DNA by the AIM2 Inflammasome Is Responsible for Production of Interleukin-1β by Virulent Suilysin-Negative Streptococcus suis Serotype 2. Pathogens 2020, 9, 147.

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