Abstract
Streptococcus suis serotype 2 is an important porcine pathogen and zoonotic agent causing sudden death, septic shock and meningitis, with exacerbated inflammation being a hallmark of the infection. A rapid, effective and balanced innate immune response against S. suis is critical to control bacterial growth without causing excessive inflammation. Even though interleukin (IL)-1 is one of the most potent and earliest pro-inflammatory mediators produced, its role in the S. suis pathogenesis has not been studied. We demonstrated that a classical virulent European sequence type (ST) 1 strain and the highly virulent ST7 strain induce important levels of IL-1 in systemic organs. Moreover, bone marrow-derived dendritic cells and macrophages contribute to its production, with the ST7 strain inducing higher levels. To better understand the underlying mechanisms involved, different cellular pathways were studied. Independently of the strain, IL-1β production required MyD88 and involved recognition via TLR2 and possibly TLR7 and TLR9. This suggests that the recognized bacterial components are similar and conserved between strains. However, very high levels of the pore-forming toxin suilysin, produced only by the ST7 strain, are required for efficient maturation of pro-IL-1β via activation of different inflammasomes resulting from pore formation and ion efflux. Using IL-1R−/− mice, we demonstrated that IL-1 signaling plays a beneficial role during S. suis systemic infection by modulating the inflammation required to control and clear bacterial burden, thus promoting host survival. Beyond a certain threshold, however, S. suis-induced inflammation cannot be counterbalanced by this signaling, making it difficult to discriminate its role.
Highlights
Streptococcus suis causes sudden death and meningitis in pigs and is responsible for important economic losses to the swine industry
IL-1β levels were scarcely detectable in plasma throughout the course of infection, including upon presentation of severe clinical signs of systemic disease, with no significant differences between strains (Figures 1A and B)
S. suis induces IL‐1 release from bone marrow‐derived dendritic cells and macrophages in a strain‐dependent manner Given the elevated levels of IL-1 produced in liver and spleen and the fact that DCs and MФ are highly important during S. suis infection [11, 14], the capacity of these cells to produce IL-1 following S. suis infection was evaluated
Summary
Streptococcus suis causes sudden death and meningitis in pigs and is responsible for important economic losses to the swine industry. It is a zoonotic agent responsible for meningitis and septic shock in Lavagna et al Vet Res (2019) 50:52 lipoteichoic acid (LTA) modifications [5]. A rapid and effective innate immune response against S. suis is critical to control bacterial growth and limit the spread of the pathogen [8]. Recognition by specialized membrane-associated or cytoplasmic receptors (pattern recognition receptors [PRRs]) mediates host immune responses by inducing mediator production via activation of nuclear factor-kappa B (NF-ĸB) and mitogenactivated protein kinases (MAPKs) [9]. Recognition of S. suis occurs via surface-associated TLR2 and, possibly, TLR4 [13], while its internalization activates the endosomal TLR7 and TLR9 [14]
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