Differential role of MyD88 signaling in Streptococcus suis serotype 2-induced systemic and central nervous system...

Streptococcus suis serotype 2 is an important porcine bacterial pathogen and a zoonotic agent responsible for sudden death, septic shock and meningitis, with exacerbated inflammation being a hallmark of the systemic and central nervous system (CNS) infections. However, S. suis serotype 2 strains are genetically and phenotypically heterogeneous, being composed of a multitude of sequence types (STs) whose virulence greatly varies. Yet, most studies have used 'classical' virulent Eurasian ST1 or ST7 strains, even though ST25 and ST28 strains account for most isolates in North America. While recognition of S. suis by innate immune cells has been associated with the myeloid differentiation primary response 88 (MyD88)-dependent Toll-like receptor (TLR) pathway in vitro, particularly surface-associated TLR2, little information is available regarding its role in vivo. This study demonstrates for the first time a differential role of MyD88 signaling in S. suis-induced systemic and CNS diseases, regardless of strain background diversity. The MyD88-dependent pathway is critical for the development of systemic disease via its role in inflammation, which subsequently controls bacterial burden. However, and differently from what has been described in vitro, TLR2 and TLR4 individually do not contribute to systemic disease, suggesting possible compensation in their absence and/or a collaborative role with other MyD88-dependent TLRs. On the other hand, CNS disease does not necessarily require MyD88 signaling and, consequently, neither TLR2 nor TLR4, suggesting a partial implication of other pathways. Finally, regardless of its notable heterogeneity, recognition of S. suis serotype 2 appears to be similar, indicating that recognized components are conserved motifs.