Role of teichoic acid choline moieties in the virulence of Streptococcus pneumoniae.
In recent reports it was shown that genetically modified choline-free strains of Streptococcus pneumoniae (D39Cho(-)licA64 and D39ChiplicB31) expressing the type II capsular polysaccharide were virtually avirulent in the murine sepsis model, in sharp contrast to the isogenic and highly virulent strains D39Cho(-) and D39Chip, which have retained the choline residues at their surface. We now demonstrate that this choline-associated virulence is independent of Toll-like receptor 2 recognition. Also, despite the lack of virulence, choline-free strains of S. pneumoniae were able to activate splenic dendritic cells, induce secretion of proinflammatory cytokines, and produce specific protective immunity against subsequent challenge. However, after this transient engagement of the immune system the choline-free bacteria were rapidly cleared from the blood, while the isogenic virulent strain D39Cho(-) continued to grow, accompanied by prolonged expression of cytokines, eventually killing the experimental animals. The critical contribution of choline residues to the virulence potential of pneumococci appears to be the role that these amino alcohol residues play in a pneumococcal immune evasion strategy, the mechanism of which is unknown at the present time.
Laboratory of Microbiology, The Rockefeller University, New York, NY 10065, USA.
Florian
F
Gehre
Radek
R
Spisek
Arun S
AS
Kharat
Phillip
P
Matthews
Anjli
A
Kukreja
Robert M
RM
Anthony
Madhav V
MV
Dhodapkar
Waldemar
W
Vollmer
Alexander
A
Tomasz
D000818:Animals; D002473:Cell Wall / Q000737:chemistry*; D002794:Choline / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D008297:Male; D051379:Mice; D011008:Pneumococcal Infections / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000276:immunology / Q000472:pathogenicity*; D016019:Survival Analysis; D013682:Teichoic Acids / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000502:physiology*
D016207:Cytokines; D013682:Teichoic Acids; D037521:Virulence Factors; D002794:Choline