Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage

Simon P. Jochems; Fernando Marcon; Beatriz F. Carniel; Mark Holloway; Elena Mitsi; Emma Smith; Jenna F. Gritzfeld; Carla Solórzano; Jesús Reiné; Sherin Pojar; Elissavet Nikolaou; Esther L. German; Angie Hyder-Wright; Helen Hill; Caz Hales; Wouter A.A de Steenhuijsen Piters; Debby Bogaert; Hugh Adler; Seher Zaidi; Victoria Connor; Jamie Rylance; Helder I. Nakaya; Daniela M. Ferreira

In the LAIV carriage+ group, 936 and 711 DEG were observed at day 2 and day 9, respectively. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/347161 doi: bioRxiv preprint 9 carriers include "Innate immune system" and "Signaling by interleukins" (IL1B, CLEC4E, CD55, Fig 6b) . To further investigate these monocytes, we performed gene 213 set enrichment analysis on the Module M1 genes using list of genes from distinct monocyte 214 subsets (Fig 6c) 40 . These genes were enriched for classical CD14+CD16-monocytes (p = 215 0.00002) and not for other monocyte subsets. Moreover, this module was enriched for genes 216 related to "chemokine receptors bind chemokines" and "interferon α /β signalling" (Fig 6d) . Type I 217 interferon has been shown to be required for the clearance of pneumococcal carriage in murine 218 models 41 and these findings suggest that their activity in monocytes might be critical for this.