In vitro characterization of the microglial inflammatory response to Streptococcus suis, an important emerging zoonotic agent of meningitis.
Streptococcus suis is an important swine and human pathogen responsible for septicemia and meningitis. In vivo research in mice suggested that in the brain, microglia might be involved in activating the inflammatory response against S. suis. The aim of this study was to better understand the interactions between S. suis and microglia. Murine microglial cells were infected with a virulent wild-type strain of S. suis. Two isogenic mutants deficient at either capsular polysaccharide (CPS) or hemolysin production were also included. CPS contributed to S. suis resistance to phagocytosis and regulated the inflammatory response by hiding proinflammatory components from the bacterial cell wall, while the absence of hemolysin, a potential cytotoxic factor, did not have a major impact on S. suis interactions with microglia. Wild-type S. suis induced enhanced expression of Toll-like receptor 2 by microglial cells, as well as phosphotyrosine, protein kinase C, and different mitogen-activated protein kinase signaling events. However, cells infected with the CPS-deficient mutant showed overall stronger and more sustained phosphorylation profiles. CPS also modulated inducible nitric oxide synthase expression and further nitric oxide production from S. suis-infected microglia. Finally, S. suis-induced NF-κB translocation was faster for cells stimulated with the CPS-deficient mutant, suggesting that bacterial cell wall components are potent inducers of NF-κB. These results contribute to increase the knowledge of mechanisms underlying S. suis inflammation in the brain and will be useful in designing more efficient anti-inflammatory strategies for meningitis.
Domínguez-Punaro
María de la Cruz
Mde L
Centre de Recherche en Infectiologie Porcine (CRIP), Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, Québec, J2S 2M2, Canada.
Segura
Mariela
M
Contreras
Irazú
I
Lachance
Claude
C
Houde
Mathieu
M
Lecours
Marie-Pier
MP
Olivier
Martin
M
Gottschalk
Marcelo
M
D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000502:physiology; D021821:Communicable Diseases, Emerging / Q000382:microbiology*; D016207:Cytokines / Q000502:physiology; D004660:Encephalitis / Q000382:microbiology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000502:physiology; D016920:Meningitis, Bacterial / Q000382:microbiology* / Q000503:physiopathology; D051379:Mice; D017628:Microglia / Q000382:microbiology* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013290:Streptococcal Infections / Q000382:microbiology*; D017011:Streptococcus suis / Q000502:physiology*; D015047:Zoonoses / Q000382:microbiology*
D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D009569:Nitric Oxide