The Treponema denticola FhbB Protein Is a Dominant Early Antigen That Elicits FhbB Variant-Specific Antibodies That Block Factor H Binding and Cleavage by Dentilisin.
The Treponema denticola FhbB protein contributes to immune evasion by binding factor H (FH). Cleavage of FH by the T. denticola protease, dentilisin, may contribute to the local immune dysregulation that is characteristic of periodontal disease (PD). Although three FhbB phyletic types have been defined (FhbB1, FhbB2, and FhbB3), the in vivo expression patterns and antigenic heterogeneity of FhbB have not been assessed. Here, we demonstrate that FhbB is a dominant early antigen that elicits FhbB type-specific antibody (Ab) responses. Using the murine skin abscess model, we demonstrate that the presence or absence of FhbB or dentilisin significantly influences Ab responses to infection and skin abscess formation. Competitive binding analyses revealed that α-FhbB Ab can compete with FH for binding to T. denticola and block dentilisin-mediated FH cleavage. Lastly, we demonstrate that dentilisin cleavage sites reside within critical functional domains of FH, including the complement regulatory domain formed by CCPs 1 to 4. Analysis of the FH cleavage products revealed that they lack cofactor activity. The data presented here provide insight into the in vivo significance of dentilisin, FhbB and its antigenic diversity, and the potential impact of FH cleavage on the regulation of complement activation.
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
Daniel P
DP
Miller
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
Lee D
LD
Oliver
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
Brittney K
BK
Tegels
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
Lucas A
LA
Reed
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
Nathaniel S
NS
O'Bier
Department of Oral Biology, State University of New York at Buffalo, Buffalo, New York, USA.
Kurni
K
Kurniyati
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
Lindsay A
LA
Faust
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
Christine K
CK
Lawson
Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA.
Anna M
AM
Allard
Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA.|Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut, USA.|Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA.
Melissa J
MJ
Caimano
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA richard.marconi@vcuhealth.org.
Richard T
RT
Marconi
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000918:Antibody Specificity / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism*; D001667:Binding, Competitive; D017242:Complement Factor H / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis; D048373:Treponema denticola / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D017242:Complement Factor H; D010447:Peptide Hydrolases; C102570:dentilisin