Abstract
Background Streptococcus suis causes invasive infections in pigs and occasionally in humans. The host innate immune system plays a major role in counteracting S. suis infections. The main components of S. suis able to activate the innate immune system likely include cell wall constituents that may be released during growth or after cell wall integrity loss, however characterization of these components is still limited.Methology/Principal FindingsA concentrated very potent innate immunity activating supernatant of penicillin-treated S. suis was SDS-PAGE fractionated and tested for porcine peripheral blood mononucleated cell (PBMC) stimulating activity using cytokine gene transcript analysis. More than half of the 24 tested fractions increased IL-1β and IL-8 cytokine gene transcript levels in porcine PBMCs. Mass spectrometry of the active fractions indicated 24 proteins including 9 lipoproteins. Genetic inactivation of a putative prolipoprotein diacylglyceryl transferase (Lgt) gene resulted in deficient lipoprotein synthesis as evidenced by palmitate labeling. The Lgt mutant showed strongly reduced activation of porcine PBMCs, indicating that lipoproteins are dominant porcine PBMC activating molecules of S. suis.Conclusion/SignificanceThis study for the first time identifies and characterizes lipoproteins of S. suis as major activators of the innate immune system of the pig. In addition, we provide evidence that Lgt processing of lipoproteins is required for lipoprotein mediated innate immune activation.
Highlights
Streptococcus suis causes severe infections in pigs, including meningitis, septicemia, endocarditis, pneumonia and arthritis
S. suis activates porcine peripheral blood mononucleated cell (PBMC) efficiently Porcine PBMCs were isolated from pig blood and incubated with S. suis and collected bacterial culture supernatant
In the present study we identified 9 S. suis lipoproteins within a fraction able to activate porcine PBMCs efficiently
Summary
Streptococcus suis causes severe infections in pigs, including meningitis, septicemia, endocarditis, pneumonia and arthritis. One group of PRRs able to sense a diverse set of bacterial PAMPs is the Toll-like receptor (TLR) family. Activation of these TLRs results in nuclear translocation of transcription factors (e.g. nuclear factor kappa B, NF-kB) which causes enhanced production of pro-inflammatory cytokines, chemokines and antimicrobial peptides. Besides these direct mechanisms to eliminate invading microbes, the innate immune system plays a decisive role in initiating and strengthening humoral and cell-mediated protection. The Lgt mutant showed strongly reduced activation of porcine PBMCs, indicating that lipoproteins are dominant porcine PBMC activating molecules of S. suis
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