Interaction of pneumococcal histidine triad proteins with human complement.
The pneumococcal histidine triad (Pht) proteins PhtA, PhtB, PhtD, and PhtE form a group of conserved pneumococcal surface proteins. Humans produce antibodies to Pht proteins upon exposure to pneumococcus, and immunization of mice has provided protective immunity against sepsis and pneumonia and reduced nasopharyngeal colonization. Pht proteins are candidates for inclusion in multicomponent pneumococcal protein vaccines. Their biological function in pneumococcal infections is not clear, but a role in complement inhibition has been suggested. We measured complement deposition on wild-type and Pht mutant strains in four genetic backgrounds: Streptococcus pneumoniae D39 (serotype 2) and R36A (unencapsulated derivative of D39) and strains of serotypes 3, 4, and 19F. PspA and PspC single and double mutants were compared to the wild-type and Pht-deficient D39 strains. Factor H binding was measured to bacterial cells, lysates, and protein antigens. Deletion of all four Pht proteins (Pht(-)) resulted in increased C3 deposition on the serotype 4 strain but not on the other strains. Pht antigens did not bind factor H, and deletion of Pht proteins did not affect factor H binding by bacterial lysates. The Pht(-) mutant serotype 4 strain bound slightly less factor H than the wild-type strain when binding was measured by flow cytometry. Pht proteins may play a role in immune evasion, but the mechanism of function is unlikely to be mediated by factor H binding. The relative contribution of Pht proteins to the inhibition of complement deposition is likely to be affected by the presence of other pneumococcal proteins and to depend on the genetic background.
Melin
Merit
M
National Institute for Health and Welfare, Department of Vaccination and Immune Protection, Mannerheimintie 166, 00300 Helsinki, Finland. merit.melin@thl.fi
Di Paolo
Emmanuel
E
Tikkanen
Leena
L
Jarva
Hanna
H
Neyt
Cecile
C
Käyhty
Helena
H
Meri
Seppo
S
Poolman
Jan
J
Väkeväinen
Merja
M
D001426:Bacterial Proteins / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism*; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000276:immunology*
D001426:Bacterial Proteins; D003176:Complement C3; C097552:histidine triad protein; D017242:Complement Factor H; D006867:Hydrolases