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

FH is a soluble protein found in human plasma that suppresses the alternative complement pathway. 18 It is well described that pneumococcus binds FH via Pneumococcal surface protein C (PspC), 19 facilitating adherence to epithelial cells. 20 PspC also interacts with the human polymeric immunoglobulin (Ig) receptor to promote bacterial adherence to, and invasion of, epithelial cells, as well as binding to the secretory component of immunoglobulin A (IgA). 21 As a result of these important interactions with the host immune system, PspC has been proposed as a vaccine candidate to block pneumococcal carriage. 22 The process of FH-mediated adherence and uptake of pneumococci has been described. The first and initial contact of FH-coated pneumococci is mediated by glycosaminoglycans expressed on the surface of human cells, and the second step, pneumococcal uptake, is integrin mediated and depends on host signaling molecules such as phosphatidylinositol 3-kinase. 23 In this study we found that a doubling in nasal FH levels was associated with a 9.3 times increase in the odds of carriage and a 4.26 times increase in the geometric mean of carriage density.