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 investigated whether the presence of virus predisposed certain individuals to colonization. There were no significant differences between virus-positive and virus-negative subjects with regard to age (22 ± 3 vs. 23 ± 7 years, P ¼ 0.5), gender (M/F 6:14 vs. 32:49, P ¼ 0.6), or inoculation dose (P ¼ 0.8). Among virus-positive subjects, 75% became colonized (15/20) as compared with 46% virus-negative subjects (37/81) (P ¼ 0.02; Figure 1a ). We could not find an association between the presence of virus and increased density (Figure 1b) or duration of 6B colonization (data not shown). Only infections caused by a single virus were detected. The detected viruses among Figure 1 Asymptomatic upper respiratory tract (URT) viral infections are associated with susceptibility to pneumococcal colonization but not increased density. (a) A total of 101 healthy subjects were screened for URT viruses by multiplex PCR 5 days before intranasal inoculation of 6B pneumococcus. The percentage of carriage-positive (carriers) and carriage-negative (noncarriers) subjects are shown for virus negative or virus positive. Among virus-positive subjects, 75% became colonized as compared with 46% virus-negative subjects (P ¼ 0.02, using Fisher's exact test). (b) Colonization density recovered from the nasopharynx was measured in nasal wash samples collected 2, 7, and 14 days following pneumococcal inoculation and is expressed as CFU ml À 1 recovered from nasal wash (NW) of virus-negative (no virus) and virus-positive (virus) groups. There was no difference in colonization density between viruspositive and virus-negative subjects. CFU, colony-forming unit; neg, negative; pos, positive. As virally infected individuals colonized with pneumococci had slightly high levels of FH, we investigated the relationship between FH and bacterial colonization density. We found that individuals with high mucosal FH levels had increased 6B colonization density (Figure 2e, P ¼ 0.005).