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

Using a generalized estimating equation (GEE) model we examined the association of virus presence and mucosal FH levels, individually as well as jointly, with carriage presence and density ( Table 1) . When we examined the effects of virus presence and mucosal FH levels individually (GEE models 1 and 2), virus presence was associated with a 2.83 times increase in the odds of becoming colonized (P ¼ 0.023) and a doubling in FH levels was associated with a 2.54 times increase in the geometric mean of carriage density (P ¼ 0.002). When we Mucosal levels of (a) Factor H, (b) secretory leukocyte proteinase inhibitor (SLPI), (c) b-defensin 2, and (d) lactoferrin were measured in nasal wash samples obtained 2 days after pneumococcal challenge with 6B. Levels are expressed in ng ml À 1 and results are stratified by pneumococcal carriage and absence or presence of virus. Statistical differences were analyzed using unpaired Student's t-test (*Pr0.05). (e) We observed a positive correlation between levels of FH and pneumococcal colonization density (CFU ml À 1 ) recovered from nasal wash (NW) 2 days after inoculation using Pearson's correlation test. CFU, colony-forming unit. P-value and the correlation coefficient (r) are presented. examined their effects jointly (GEE model 3), we found an interaction. Specifically, among virus positives a doubling in FH levels was associated with a 9.33 times increase in the odds of carriage (P ¼ 0.034) and a 4.26 times increase in the geometric mean of carriage density (P ¼ 0.009).