title: Factor H binding to PspC of Streptococcus pneumoniae increases adherence to human cell lines in vitro and enhances invasion of mouse lungs in vivo.
abstract: Pneumococcal surface protein C (PspC) binds to both human secretory immunoglobulin A (sIgA) and complement factor H (FH). FH, a regulator of the alternative pathway of complement, can also mediate adherence of different host cells. Since PspC contributes to adherence and invasion of host cells, we hypothesized that the interaction of PspC with FH may also mediate adherence of pneumococci to human cells. In this study, we investigated FH- and sIgA-mediated pneumococcal adherence to human cell lines in vitro. Adherence assays demonstrated that preincubation of Streptococcus pneumoniae D39 with FH increased adherence to human umbilical vein endothelial cells (HUVEC) 5-fold and to lung epithelial cells (SK-MES-1) 18-fold, relative to that of D39 without FH on the surface. The presence of sIgA enhanced adherence to SK-MES-1 6-fold and to pharyngeal epithelial cells (Detroit 562) 14-fold. Furthermore, sIgA had an additive effect on adherence to HUVEC; specifically, preincubation of D39 with both FH and sIgA led to a 21-fold increase in adherence. Finally, using a mouse model, we examined the significance of the FH-PspC interaction in pneumococcal nasal colonization and lung invasion. Mice intranasally infected with D39 preincubated with FH had increased bacteremia and lung invasion, but they had similar levels of nasopharyngeal colonization compared to that of mice challenged with D39 without FH.
authors.affiliation: Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Quin
authors.forename: Chinwendu
authors.initials: C
authors.lastname: Onwubiko
authors.forename: Quincy C
authors.initials: QC
authors.lastname: Moore
authors.forename: Megumi Fujioka
authors.initials: MF
authors.lastname: Mills
authors.forename: Larry S
authors.initials: LS
authors.lastname: McDaniel
authors.forename: Stephanie
authors.initials: S
authors.lastname: Carmicle
mesh_terms: D000818:Animals; D016470:Bacteremia; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D015169:Colony Count, Microbial; D017242:Complement Factor H / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D008168:Lung / Q000382:microbiology*; D051379:Mice; D008808:Mice, Inbred CBA; D011018:Pneumonia, Pneumococcal / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D007071:Immunoglobulin A, Secretory; C110344:SpsA protein, Streptococcus pneumoniae; D017242:Complement Factor H