Colonization of CF patients’ upper airways with S. aureus contributes more decisively to upper airway inflammation than P. aeruginosa

Abstract

In cystic fibrosis (CF) patients' airways, inflammatory processes decisively contribute to remodeling and pulmonary destruction. The aims of this study were to compare upper airway (UAW) inflammation in the context of Staphylococcus aureus and Pseudomonas aeruginosa colonization in a longitudinal setting, and to examine further factors influencing UAW inflammation. Therefore, we analyzed soluble inflammatory mediators in noninvasively obtained nasal lavage (NL) of CF patients together with microbiology, medication, and relevant clinical parameters. NL, applying 10 mL of isotonic saline per nostril, was serially performed in 74 CF patients (326 samples). Concentrations of the inflammatory mediators' interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP)-9, and its anti-protease TIMP-1 were quantified by bead-based multiplexed assay, neutrophil elastase (NE) via ELISA. Culture-based microbiology of the upper and lower airways (LAW), as well as serological and clinical findings, were compiled. Our results indicate that UAW colonization with S. aureus significantly impacts the concentration of all measured inflammatory mediators in NL fluid except TIMP-1, whereas these effects were not significant for P. aeruginosa. Patients with S. aureus colonization of both the UAW and LAW showed significantly increased concentrations of IL-1β, IL-6, IL-8, MMP-9, and slightly elevated concentrations of NE in NL fluid compared to non-colonized patients. This work elaborates a survey on S. aureus' virulence factors that may contribute to this underestimated pathology. Serial assessment of epithelial lining fluid by NL reveals that colonization of the UAW with S. aureus contributes more to CF airway inflammatory processes than hitherto expected.

Increased cytokines in cystic fibrosis patients’ upper airways during a new P. aeruginosa colonization

“…Concurrent co‐colonization with SA in either UAW or LAW did not influence NL cytokine dynamics upon de novo acquisition of PsA (Figure C). Of note, in a recent study we identified SA to contribute more decisively to UAW inflammation than PsA . Indeed, cytokine concentrations in NL were higher when SA was present, what mainly applied to the PsA‐free patients.…”

The SaeRS Two-Component System Controls Survival of Staphylococcus aureus in Human Blood through Regulation of Coagulase

“…This suggests that SaeRS may play different roles in different stages of host cell-pathogen interactions. Several key steps of infection include bacterial colonization, proliferation, evasion of innate defenses, and cytotoxicity (Ji et al, 1999; Okumura and Nizet, 2014; Janhsen et al, 2016; McGuinness et al, 2016). It was clearly demonstrated that SaeRS is critical for S. aureus to adhere to and invade human epithelial and endothelial cells through regulation of adhesins and invasins (Giraudo et al, 1999; Liang et al, 2006; Sun et al, 2010).…”

The Upper Airway Microbiota, Environmental Exposures, Inflammation, and Disease

“…Disease states that drive UA chronic inflammation, such as cystic fibrosis (CF), obstructive sleep apnea, CRS, and asthma, also impact the UA inflammatory profile and microbiota [ 65 ]. CF patients with higher colonization of S. aureus within their UAs had distinct levels of inflammatory biomarkers in nasal lavage samples [ 65 ]. Notable levels of IL-6, IL-8, IL-1β, MMP-9, and neutrophil elastase were detected [ 65 ].…”

“…CF patients with higher colonization of S. aureus within their UAs had distinct levels of inflammatory biomarkers in nasal lavage samples [ 65 ]. Notable levels of IL-6, IL-8, IL-1β, MMP-9, and neutrophil elastase were detected [ 65 ]. This suggests that increased colonization of S. aureus in diseased UAs could further contribute to the inflammatory response [ 65 ].…”

“…Notable levels of IL-6, IL-8, IL-1β, MMP-9, and neutrophil elastase were detected [ 65 ]. This suggests that increased colonization of S. aureus in diseased UAs could further contribute to the inflammatory response [ 65 ]. S. aureus in low-infection colony numbers triggers the secretion of the anti-inflammatory cytokine IL-10, yet when present in higher colony numbers, it reduces IL-10, leading to a more proinflammatory response [ 65 , 66 , 67 ].…”