Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage.
Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection.
Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.
S
S
Glennie
Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.
J F
JF
Gritzfeld
Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.
S H
SH
Pennington
Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.
M
M
Garner-Jones
Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.
N
N
Coombes
Liverpool Specialist Virology Centre, Royal Liverpool and Broadgreen University Hospital, Liverpool, UK.
M J
MJ
Hopkins
Centro de Biotecnologia, Instituto Butantan, Sao Paulo, Brazil.
C F
CF
Vadesilho
Centro de Biotecnologia, Instituto Butantan, Sao Paulo, Brazil.
E N
EN
Miyaji
Tropical Clinical Trial Unit, Liverpool School of Tropical Medicine, Liverpool, UK.
D
D
Wang
Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.|NIHR Royal Liverpool and Broadgreen University Hospital NHS Trust, Liverpool, UK.
A D
AD
Wright
Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.|NIHR Royal Liverpool and Broadgreen University Hospital NHS Trust, Liverpool, UK.
A M
AM
Collins
Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.
S B
SB
Gordon
Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.
D M
DM
Ferreira
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites; D060085:Coinfection; D017242:Complement Factor H / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D018604:Epitope Mapping; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009305:Nasopharynx / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D011485:Protein Binding; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology / Q000821:virology; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity; D014777:Virus Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C110344:SpsA protein, Streptococcus pneumoniae; D017242:Complement Factor H