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

Pneumococcal colonization at the mucosal surface is a prerequisite of invasive disease. 6, 7 Children with radiologically confirmed pneumonia have a marked increase in the density of colonizing pneumococci if coinfected with influenza A, respiratory syncytial virus, or rhinovirus. 3 Several possible mechanisms may account for increased nasopharyngeal pneumococcal density, including influenza-induced damage to the epithelium and/or alterations in host cellular responses to bacterial pathogens. 8, 9 Viral infections reduce mucociliary velocity, denude epithelial surfaces and expose basement membranes, and modulate chemokine and innate defenses. [10] [11] [12] We used an experimental human pneumococcal carriage (EHPC) model 13 to investigate the relationship between asymptomatic URT viral infections and pneumococcal colonization in humans. Experimental carriage offers a unique opportunity to investigate mucosal responses 14, 15 in a setting where the onset and termination as well as density of pneumococcal carriage episodes are known. 16, 17 In this study, we hypothesized that subjects with an asymptomatic URT viral infection would be more susceptible to pneumococcal carriage acquisition and/or would have increased carriage density. We observed that virus was associated with a 2.8-fold increase in the odds of becoming colonized after experimental inoculation. We then investigated a possible mechanism by which virus could modulate mucosal defenses and increase colonization. We measured levels of several soluble innate factors at the nasal mucosa and observed that levels of human Factor H (FH) were increased in subjects coinfected with virus and pneumococcus.