Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage

Glennie, S; Gritzfeld, J F; Pennington, S H; Garner-Jones, M; Coombes, N; Hopkins, M J; Vadesilho, C F; Miyaji, E N; Wang, D; Wright, A D; Collins, A M; Gordon, S B; Ferreira, D M

We used a pneumococcal strain lacking expression of PspC (D39 DPspC) to show that PspC mediates the effect of FH on epithelial adherence. Although D39 expresses PspC3 and the 6B strain used for human inoculation expresses PspC9, there is 58% similarity in the N-terminal (first 110 amino acids) between the PspC amino acid sequence of both strains. With D39, increased adherence promoted by nasal wash was not caused by existing FH alone in these samples. We observed no difference in adherence when nasal wash samples depleted of IgG or IgA were used to treat D39 DPspC and therefore the PspC-secretory IgA interaction was not the main mechanism for this increased adherence either. There are several pneumococcal-specific host-pathogen interactions that could play a role in epithelial attachment. 30 The interaction between PspC and vitronectin has recently been highlighted as an important mechanism for pneumococcal adhesion. 31 We hypothesize that in the presence of anti-PspC IgG and low levels of FH, there is decreased pneumococcal adherence as anti-PspC antibodies block adherence mediated by other factors such as vitronectin (Figure 6 , middle). FH continues to facilitate low levels of adherence because human anti-PspC antibodies do not recognize the FH binding site. When FH levels are high, pneumococcal adherence increases because of more interactions between PspC and FH ( Figure 6 , right). Decreased adherence caused by the binding of anti-PspC antibodies to other factors such as vitronectin is masked by this increase in Pspc-FH binding and adherence.