Lgt Processing Is an Essential Step in Streptococcus suis Lipoprotein Mediated Innate Immune Activation

P.J. Wichgers Schreur, J.M.J. Rebel, M.A. Smits, J.P.M. van Putten, H.E. Smith

    Research output: Contribution to journalArticleAcademicpeer-review

    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 Findings: A 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-1b 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/Significance: This 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.
    Original languageEnglish
    Article numbere22299
    Number of pages11
    JournalPLoS One
    Volume6
    Issue number7
    DOIs
    Publication statusPublished - 2011

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