Abstract

Pseudomonas aeruginosa (PA) is the key bacterial pathogen in adult cystic fibrosis (CF) lung disease. We investigated how PA changes the response of primary bronchial epithelial cells (pBECs) to human rhinovirus (HRV) infections. Differentiated pBECs were infected with PA for 16 days and then infected with HRV. We performed a quantitative proteomic analysis and quantified Cytokines and viral RNA by cytometric bead array (CBA) and qPCR. In total 6500 proteins were detected. HRV infection led to increased abundance of 50 proteins in CF and 44 proteins in healthy control (HC) cells, mainly interferon-induced and antigen-presenting proteins. Compared to HRV infection, coinfection with PA and HRV increased abundance of 25 host proteins in HC and lowered levels of 5 proteins. In CF, additional proteins were detected with differential abundance. Host proteins with increased abundance were linked to IL-1ß production (CARD8, ZFP91) and pathogen internalization (CAV1, NDRG1), while abundance of proteins with functions in immunity (HLA-B, TLR2), epithelial repair (DDR1) and ciliary movement (CFAP70) was decreased. CBA analysis unveiled that compared to HRV alone, coinfection with PA drastically decreased IL-6 protein but not mRNA, and increased IL-1β concentrations. Recombinant IL-6 was degraded in a serine-protease dependent manner when treated with conditioned medium from coinfections, but not from single infections. Neither IL-8, IP-10, TNF-α protein, IFN-β/λ-1 mRNA, nor viral load differed significantly between HRV-infected and coinfected cells. Our analysis highlights differences in host and bacterial responses in coinfections, distinct from changes induced by single pathogens.

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