Étude de la pathogenèse de l’infection et de l’inflammation causées par des souches de Streptococcus suis de différentes origines

Streptococcus suis is one of the most important porcine bacterial pathogens and is responsible for substantial economic losses to the swine industry. Moreover, it is also a zoonotic agent representing serious risks to human health. This bacterium causes a variety of pathologies, of which meningitis, sudden death, and septic shock are the most frequent, and which are the consequence of an exacerbated inflammation that characterizes the systemic and central nervous system (CNS) infections. Of the different classification systems, serotyping and multilocus sequence typing are the two most commonly used for S. suis. Though 35 serotypes exist, nearly all studies have used "classical" European and/or Asian serotype 2 sequence type (ST) 1 or 7 strains, regardless of the fact that S. suis is a highly heterogenous bacterium, both genetically and phenotypically. As such, our knowledge is based almost exclusively on these strains, yet it has been extrapolated to the entire S. suis population. This demonstrates the clear lack of information on the role of S. suis components from different origins in its virulence and pathogenesis, as well as in the induced inflammatory response. Consequently, the main objective of this thesis was to better understand the pathogenesis of the infection and the inflammation caused by S. suis using different strains and to evaluate the impact of these differences on pathogenesis and inflammation. Firstly, we demonstrated that surface components, including the capsular polysaccharide, antigen I/II, and lipoteichoic acids, as well as their roles and properties, may vary according to the origin of the strain used (serotype, ST, geographical isolation) due to differences in genetic background and phenotypic characteristics. Furthermore, the choice of strain and experimental model can introduce an important bias in virulence and pathogenesis studies that can affect the conclusions reached. Alongside, we demonstrated that systemic compartment host cells recognize conserved components of S. suis via the Toll-like receptor pathway and downstream MyD88-dependent signaling, which leads to the induction of an inflammatory response in which blood monocytes and neutrophils participate. However, the magnitude of this response is modulated by the genetic background and phenotypic characteristics of the strain. Though beneficial for the host, the induced inflammation must be controlled, as too little inflammation allows the bacteria to replicate, while exacerbated inflammation causes tissue and organ damage. Indeed, these two outcomes may result in host death. Finally, the CNS is extremely sensitive to S. suis infection and quickly and aggressively responds to its presence via an exacerbated inflammatory response that will remain localized and that is, more often than not, detrimental to the host. However, recognition of S. suis in the CNS does not necessarily require MyD88-dependent signaling. Moreover, infiltration of blood monocytes and neutrophils is a consequence of the induced inflammation, which indicates that resident cells are responsible for this response, though the leptomeninges do not appear to greatly participate therein.

Keyphrases: Streptococcus suis, Serotype, Sequence type, Virulence factor, Systemic infection, Central nervous system infection, Inflammatory response, Septic shock, Meningitis, Mouse model