Reduced Glycolysis and Cytotoxicity in Staphylococcus aureus Isolates from Chronic Rhinosinusitis as Strategies for Host Adaptation.

Chronic rhinosinusitis (CRS) is a multifactorial infection of the nasal cavity and sinuses. In this study, nasal swabs from control donors (N = 128) and patients with CRS (N = 246) were analysed. Culture methods and metagenomics revealed no obvious differences in the composition of the bacterial communities between the two groups. However, at the functional level, several metabolic pathways were significantly enriched in the CRS group compared to the control group. Pathways such as carbohydrate transport metabolism, ATP synthesis, cofactors and vitamins, photosynthesis and transcription were highly enriched in CRS. In contrast, pathways related to lipid metabolism were more representative in the control microbiome. As S. aureus is one of the main species found in the nasal cavity, staphylococcal isolates from control and CRS samples were analysed by microarray and functional assays. Although no significant genetic differences were detected by microarray, S. aureus from CRS induced less cytotoxicity to lung cells and lower rates of glycolysis in host cells than control isolates. These results suggest the differential modulation of staphylococcal virulence by the environment created by other microorganisms and their interactions with host cells in control and CRS samples. These changes were reflected in the differential expression of cytokines and in the expression of Agr, the most important quorum-sensing regulator of virulence in S. aureus. In addition, the CRS isolates remained stable in their cytotoxicity, whereas the cytotoxic activity of S. aureus isolated from control subjects decreased over time during in vitro passage. These results suggest that host factors influence the virulence of S. aureus and promote its adaptation to the nasal environment during CRS.

Age-related changes of the innate immune system of the palatine tonsil in a healthy cohort.

Although tonsillectomy is performed frequently, the role of palatine tonsils in life long immune protection or tolerance is still debated and the consequences of their removal for the immune system are of general interest. We analysed the tonsillar myeloid compartment in healthy subjects across a wide range of age (64% male; age range: 3 - 85 years) and compared its composition to the peripheral blood. We could observe a strong accumulation of all granulocyte subsets in the aging tonsil, which was most pronounced for basophils and mast cells. On functional level, an increase of CD163 and CD206 expression among monocytes and an increase of neutrophils expressing the inhibitory FcγRIIb correlated with increasing age. While the age-related shift of the leukocyte composition towards monocytes in blood is not reflected in tonsils, the increasing immunoregulatory phenotype of tonsilar monocytes is potentially counteracting the phenomenon of inflammaging at higher age.