The lack of Pneumococcal surface protein C (PspC) increases the susceptibility of Streptococcus pneumoniae to the killing by microglia.
Microglial cells, the resident phagocytes in the brain, share many phenotypical and functional characteristics with peripheral macrophages, suggesting that they may participate in an innate immune response against microorganisms invading the central nervous system (CNS). In this study, we demonstrate that the microglial cells constitutively exhibit antibacterial activity in vitro against Streptococcus pneumoniae. By using a Pneumococcal surface protein C (PspC)-deleted strain and its wild-type counterpart, we found that the extent of such an activity is significantly influenced by the presence of a PspC molecule on the bacterial surface. The PspC- mutant FP20 is indeed more susceptible than the PspC+ strain HB565 to microglial killing. Interestingly, this phenomenon is observed when using a medium supplemented with heat-inactivated foetal bovine serum (FBS). Electron microscopy studies indicate that the microglial cells interact more efficiently with PspC- than with PspC+ pneumococci. Moreover, upon infection with the PspC- mutant, microglial cells produce levels of TNF-alpha, MIP-2, IL-10 and nitric oxide, significantly higher than those observed with PspC+ bacteria. These findings indicate that the lack of PspC significantly enhances the susceptibility of S. pneumoniae to both bactericidal activity and secretory response by the microglial cells, suggesting that this molecule may play an important role in the invasion of CNS by pneumococcus.
Peppoloni
Samuele
S
Hygiene, Microbiology and Biostatistics Department, University of Modena and Reggio Emilia, 41100 Modena, Italy. peppoloni.samuele@unimore.it
Colombari
Bruna
B
Neglia
Rachele
R
Quaglino
Daniela
D
Iannelli
Francesco
F
Oggioni
Marco Rinaldo
MR
Pozzi
Gianni
G
Blasi
Elisabetta
E
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis; D015169:Colony Count, Microbial; D017353:Gene Deletion; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D050296:Microbial Viability; D017628:Microglia / Q000276:immunology* / Q000382:microbiology* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009569:Nitric Oxide / Q000096:biosynthesis; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000954:Antigens, Surface; D001426:Bacterial Proteins; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide