Contact-Free Co-Culture Model for the Study of Innate Immune Cell Activation During Respiratory Virus Infection

The early interactions between the nasal epithelial layer and the innate immune cells during viral infections remains an under-explored area. The ...

University of Helsinki

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catalyzing enzyme. It has been suggested that it has a role in lower airway allergic inflammations, but its role in allergic rhinitis has not been investigated.

Indoleamine 2,3-dioxygenase expression in patients with allergic rhinitis: a case-control study.

Background. Endoscopic sinus surgery (ESS) is considered for chronic rhinosinusitis (CRS) after failure of conservative therapy. Objective. The aim of this study was to evaluate endoscopically ostium patency and mucosal recovery after ESS, with either maxillary sinus ostium-preserving or -enlarging techniques. Materials and Methods. Thirty patients with non-polypous CRS were enrolled. Uncinectomy-only and additional middle meatal antrostomy were randomly and single-blindly performed for each side. Pre- and postoperative endoscopic scores were semi-quantitatively determined according to findings in the ostiomeatal complex area. Adhesions, maxillary sinus mucosal swelling, secretions, and ostium obstruction were also endoscopically evaluated. In addition, symptoms were asked and computed tomography scans were taken preoperatively and 9 months postoperatively. Results. At 16 days postoperatively, a better endoscopic score and a less obstructed ostium were found with antrosomy. At 9 months postoperatively the endoscopic score improved significantly and identically with both procedures, however, obstructed ostia and sinus mucosal swelling/secretions were insignificantly more frequently found on the uncinectomy-only side. Endoscopic and radiologic findings of the maxillary sinus mucosa and ostium correlated significantly 9 months postoperatively. Conclusion. There was a good long-term mucosal recovery with both surgical procedures. In terms of early mucosal recovery and ostium patency, antrostomy might be slighly superior.

Endoscopic sinus surgery with antrostomy has better early endoscopic recovery in comparison to the ostium-preserving technique.

Chronic rhinosinusitis (CRS) is an inflammation of the nose and paranasal sinuses lasting for ≥12 weeks. Endoscopic sinus surgery (ESS) is considered during difficult to treat CRS. The minimally invasive technique focuses on the transition areas rather than on the ostia. The aim of this study was to evaluate symptoms, the number of acute sinusitis episodes, and satisfaction after ESS with either preservation or enlargement of the maxillary sinus ostium. Thirty patients with moderate nonpolypous CRS were enrolled. Uncinectomy only and additional middle meatal antrostomy were randomized for each side of each patient and performed single blindly. The symptoms questionnaires were filled at four time intervals. Significant symptom reduction was achieved independently of operation technique. The number of acute sinusitis episodes indicating the exacerbation rate decreased significantly at 9 and, on average, 68 months postoperatively. However, the exacerbation rate began to increase after 9 months postoperatively. Three revisions were performed on the side with uncinectomy only and one on the side with additional antrostomy. Most patients reported good satisfaction with both procedures. There was a trend for patients with asthma and/or job exposure to report insignificantly more frequently no satisfaction with surgery, especially with the uncinectomy-only procedure. Both procedures seem to be efficient in providing symptom relief and satisfaction. More studies are needed to evaluate if patients with risk factors benefit more from an ostium-enlarging procedure.

Satisfaction with maxillary sinus surgery might be influenced by risk factors.

Conclusion IDO might be useful for predicting progression of primary tumor stage T2 and T3 in tongue squamous cell carcinoma (TSCC), but does not seem like a specific biomarker for diagnosing TSCC and predicting patient survival. Objectives Indoleamine 2,3-dioxygenase (IDO) is expressed in many cells and it catabolises the essential amino acid tryptophan to kynurenine. IDO acts as an immune modulator through suppression of T-cell immunity and other pathways. In cancer cells, IDO has been proposed to promote tumor progression by enabling malignant cells to escape from the immune system. The aim of this study was to evaluate the association and prognostic relevance of IDO expression in TSCC. Method One hundred and eight retrospective tongue and lymph node specimens were stained immunohistochemically with monoclonal antibody anti-indoleamine 2,3-dioxygenase. The relative abundance of IDO positive epithelial cells, IDO staining intensity, and inflammation were assessed semi-quantitatively with light microscopy. Results IDO was expressed stronger in tongue hyperplasia than in TSCC. However, IDO expression associated with poor survival in the sub-groups with primary tumor stage T2-T4 and in the sub-group with strong inflammation in tumors' invasive front. 

The expression and prognostic relevance of indoleamine 2,3-dioxygenase in tongue squamous cell carcinoma.

The study suggests that cancerous inhibitor of protein phosphatase 2A (CIP2A) expression and eosinophilia associate with chronic rhinosinusitis with nasal polyps with aspirin exacerbated respiratory disease (CRSwNP + AERD). Further studies with a larger sample size are needed to evaluate further the role of CIP2A and related pathways in CRSwNP + AERD.

The expression of cancerous inhibitor protein phosphatase 2A in chronic rhinosinusitis with nasal polyps.

 We established an  co-culture model involving H3N2-infection of human nasal epithelium with peripheral blood mononuclear cells (PBMC) to investigate their cross-talk during early H3N2 infection.  Nasal epithelium was differentiated from human nasal epithelial stem/progenitor cells and cultured wtih fresh human PBMC. PBMC and supernatants were harvested after 24 and 48 h of co-culture with H3N2-infected nasal epithelium. We used flow cytometry and Luminex to characterize PBMC subpopulations, their activation and secretion of cytokine and chemokines.  H3N2 infection of the nasal epithelium associated with significant increase in interferons (IFN-α, IFN-γ, IL-29), pro-inflammatory cytokines (TNF-α, BDNF, IL-3) and viral-associated chemokines (IP-10, MCP-3, I-TAC, MIG), detectable already after 24 h. This translates into rapid activation of monocytes, NK-cells and innate T-cells (MAIT and γδ T cells), evident with CD38+ and/or CD69+ upregulation.  This system may contribute to  mechanistic immunological studies bridging systemic models and possibly enable the development of targeted immunomodulatory therapies.

A Co-culture Model of PBMC and Stem Cell Derived Human Nasal Epithelium Reveals Rapid Activation of NK and Innate T Cells Upon Influenza A Virus Infection of the Nasal Epithelium.

Inflammatory upper airway diseases cause significant morbidity. They include phenotypes with different treatment; allergic or non-allergic rhinitis (AR, nAR), and chronic rhinosinusitis with or without nasal polyps (CRSwNP, CRSsNP). In clinical practice, these phenotypes are often difficult to distinguish and may overlap.

Hierarchical clustering in evaluating inflammatory upper airway phenotypes; increased symptoms in adults with allergic multimorbidity.

Allergic rhinitis, chronic rhinosinusitis, and asthma are highly prevalent, multifactorial chronic airway diseases. Several environmental and genetic factors affect airway epithelial dynamics leading to activation of inflammatory mechanisms in the airways. This review links environmental factors to host epithelial immunity in airway diseases. Understanding altered homeostasis of the airway epithelium might provide important targets for diagnostics and therapy of chronic airway diseases.

Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases.

Environmental tobacco smoke (ETS) exposure increases asthma risk in children. There is limited knowledge of prenatal ETS for adult-onset asthma.

Annika Luukkainen

Haartman Institute,
Medicum,
Haartman Institute, Medicum

University of Helsinki

Contact-Free Co-Culture Model for the Study of Innate Immune Cell Activation During Respiratory Virus Infection

Annika Luukkainen

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University of Helsinki

Contact-Free Co-Culture Model for the Study of Innate Immune Cell Activation During Respiratory Virus Infection

Haartman Institute,
Medicum,
Haartman Institute, Medicum