Staphylococcus aureus Biofilm-Secreted Factors Cause Mucosal Damage, Mast Cell Infiltration, and Goblet Cell Hyperplasia in a Rat Rhinosinusitis Model
Abstract
:1. Introduction
2. Results
2.1. Long-Term SABSF Challenges Induce Multifocal Inflammation
2.2. Long-Term SABSF Challenges of Nasal Mucosa Induce Eosinophilic Infiltration
2.3. Long-Term SABSF Challenges Induce Mucosal Damage and Goblet Cell Hyperplasia of the Nasal Mucosa
2.4. Long-Term SABSF Challenges Induce Mastocytosis in the Nasal Mucosa
2.5. Transcriptome Profiling by RNA-Seq Reveals Differential Inflammation between SABSF Groups
2.6. Long-Term SABSF Challenges Induce Transcription of IgA and IgG
2.7. Virulence Factors Present in the Bacterial Genome
3. Discussion
4. Materials and Methods
4.1. S. aureus Clinical Isolates
4.2. CRS Endotype Confirmation
4.3. S. aureus Biofilm-Secreted Factors
4.4. Animals and Study Design
4.5. Tissue Collection
4.6. Histological Staining
4.7. Histological Analysis
4.8. RNA Extraction
4.9. Library Preparation and Sequencing
4.10. Transcriptomic Quantification
4.11. Immunoglobulin Quantification
4.12. Bioinformatics of Transcriptomics
4.13. Bacterial Genome Sequencing
4.14. Statistics
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
CRS | chronic rhinosinusitis |
CRSsNP | CRS without nasal polyps |
CRSwNP | CRS with nasal polyps |
DEG | differentially expressed genes |
GSEA | gene set enrichment |
H&E | haematoxylin and eosin |
IHC-IF | immunohistochemistry staining using immunofluorescence detection |
IL | interleukin |
MFUs | McFarland Units |
NALT | nasal-associated lymphoid tissue |
PAS | periodic acid–Schiff |
Rcf | relative centrifugal force |
RIN | RNA integrity number |
ROI | regions of interest |
s.e.m | standard error of the mean |
SABSF | S. aureus biofilm-secreted factors |
Th | T-helper |
TSLP | thymic stromal lymphopoietin |
T2 | type 2 |
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Score | 1 | 2 | 3 | 4 |
Mast cell infiltration | Less than 5 non-clustered mast cells were observed in turbinates, lateral nasal walls, or septum mucosa. | 5 to 15 non-clustered mast cells were observed within turbinates, lateral walls, or septum mucosa. | Less than 3 clusters (5 cells) of the mast were observed within the mucosa of turbinates, lateral walls, or septum. | More than 3 clusters of mast cells were observed within the mucosa of turbinates, lateral walls, or septum. |
Score | 1 | 2 | 3 | 4 |
Mucosal damage | Less than 3 regions of erosion, ulceration, or necrosis were observed within turbinates, lateral nasal walls, or septum mucosa. | 3–6 areas showed exfoliation of the superficial epithelium within the mucosa of turbinates, lateral wall, or septum. | More than 6 regions were observed with epithelial erosion, or less than 6 regions with total loss of epithelium and basement membrane with exposure of the underlying submucosa were observed. | More than 6 regions with complete loss of epithelium and basement membrane were observed, accompanied by exposure of the underlying submucosa and necrosis. |
Score | 1 | 2 | 3 | 4 |
Goblet cell hyperplasia | 3 or fewer regions were observed with goblet cell hypertropia or hyperplasia within turbinates, lateral nasal walls, or septum mucosa. | 3–6 areas with regions were observed with increased numbers of goblet cells and pseudocrypt formation within the mucosa of turbinates, lateral walls, or septum. | More than 6 regions were observed with increased numbers of goblet cells with pseudocrypt formation within the mucosa of turbinates, lateral walls, or septum. | Increased cellularity and disorganisation of the respiratory epithelium were observed, accompanied by hyperplasia of goblet cells within the mucosa of turbinates, lateral wall, or septum. |
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Houtak, G.; Nepal, R.; Bouras, G.; Shaghayegh, G.; Bennett, C.; Finnie, J.; Fenix, K.; Psaltis, A.J.; Wormald, P.-J.; Vreugde, S. Staphylococcus aureus Biofilm-Secreted Factors Cause Mucosal Damage, Mast Cell Infiltration, and Goblet Cell Hyperplasia in a Rat Rhinosinusitis Model. Int. J. Mol. Sci. 2024, 25, 3402. https://doi.org/10.3390/ijms25063402
Houtak G, Nepal R, Bouras G, Shaghayegh G, Bennett C, Finnie J, Fenix K, Psaltis AJ, Wormald P-J, Vreugde S. Staphylococcus aureus Biofilm-Secreted Factors Cause Mucosal Damage, Mast Cell Infiltration, and Goblet Cell Hyperplasia in a Rat Rhinosinusitis Model. International Journal of Molecular Sciences. 2024; 25(6):3402. https://doi.org/10.3390/ijms25063402
Chicago/Turabian StyleHoutak, Ghais, Roshan Nepal, George Bouras, Gohar Shaghayegh, Catherine Bennett, John Finnie, Kevin Fenix, Alkis James Psaltis, Peter-John Wormald, and Sarah Vreugde. 2024. "Staphylococcus aureus Biofilm-Secreted Factors Cause Mucosal Damage, Mast Cell Infiltration, and Goblet Cell Hyperplasia in a Rat Rhinosinusitis Model" International Journal of Molecular Sciences 25, no. 6: 3402. https://doi.org/10.3390/ijms25063402