Human factor H interacts selectively with Neisseria gonorrhoeae and results in species-specific complement evasion
Department of Medicine, Division of Infectious Diseases and Immunology
Amino Acid Motifs; Animals; Blood Bactericidal Activity; Complement Factor H; Complement Inactivator Proteins; Complement Pathway, Classical; Host-Pathogen Interactions; Humans; Lipopolysaccharides; Macaca mulatta; Mice; Neisseria gonorrhoeae; Oligosaccharides; Pan troglodytes; Papio; Peptide Fragments; Porins; Protein Binding; Species Specificity
Life Sciences | Medicine and Health Sciences
Complement forms a key arm of innate immune defenses against gonococcal infection. Sialylation of gonococcal lipo-oligosaccharide, or expression of porin 1A (Por1A) protein, enables Neisseria gonorrhoeae to bind the alternative pathway complement inhibitor, factor H (fH), and evade killing by human complement. Using recombinant fH fragment-murine Fc fusion proteins, we localized two N. gonorrhoeae Por1A-binding regions in fH: one in complement control protein domain 6, the other in complement control proteins 18-20. The latter is similar to that reported previously for sialylated Por1B gonococci. Upon incubation with human serum, Por1A and sialylated Por1B strains bound full-length human fH (HufH) and fH-related protein 1. In addition, Por1A strains bound fH-like protein 1 weakly. Only HufH, but not fH from other primates, bound directly to gonococci. Consistent with direct HufH binding, unsialylated Por1A gonococci resisted killing only by human complement, but not complement from other primates, rodents or lagomorphs; adding HufH to these heterologous sera restored serum resistance. Lipo-oligosaccharide sialylation of N. gonorrhoeae resulted in classical pathway regulation as evidenced by decreased C4 binding in human, chimpanzee, and rhesus serum but was accompanied by serum resistance only in human and chimpanzee serum. Direct-binding specificity of HufH only to gonococci that prevents serum killing is restricted to humans and may in part explain species-specific restriction of natural gonococcal infection. Our findings may help to improve animal models for gonorrhea while also having implications in the choice of complement sources to evaluate neisserial vaccine candidates.
DOI of Published Version
J Immunol. 2008 Mar 1;180(5):3426-35.
Journal of immunology (Baltimore, Md. : 1950)
Ngampasutadol, Jutamas; Ram, Sanjay; Gulati, Sunita; Agarwal, Sarika; Li, Chongqing; Visintin, Alberto; Monks, Brian G.; Madico, Guillermo E.; and Rice, Peter A., "Human factor H interacts selectively with Neisseria gonorrhoeae and results in species-specific complement evasion" (2008). Open Access Articles. 2002.