Interferon inducible GBPs restrict Burkholderia thailandensis motility induced cell-cell fusion.

Innate immunity responds to pathogens by producing alarm signals and activating pathways that make host cells inhospitable for pathogen replication. The intracellular bacterium Burkholderia thailandensis invades the cytosol, hijacks host actin, and induces cell fusion to spread to adjacent cells, forming multinucleated giant cells (MNGCs) which promote bacterial replication. We show that type I interferon (IFN) restricts macrophage MNGC formation during B. thailandensis infection. Guanylate-binding proteins (GBPs) expressed downstream of type I IFN were required to restrict MNGC formation through inhibition of bacterial Arp2/3-dependent actin motility during infection. GTPase activity and the CAAX prenylation domain were required for GBP2 recruitment to B. thailandensis, which restricted bacterial actin polymerization required for MNGC formation. Consistent with the effects in in vitro macrophages, Gbp2-/-, Gbp5-/-, GbpChr3-KO mice were more susceptible to intranasal infection with B. thailandensis than wildtype mice. Our findings reveal that IFN and GBPs play a critical role in restricting cell-cell fusion and bacteria-induced pathology during infection.

Fish nasal immunity: From mucosal vaccines to neuroimmunology.

Like terrestrial vertebrates, bony fishes have a nasopharynx-associated lymphoid tissue (NALT) that protects the host against invading pathogens. Despite nasal immunity being a relatively new field in fish immunology, the investigation of nasal immune systems has already illuminated fundamental aspects of teleost mucosal immune systems as well as neuroimmunology. In this review, we highlight the importance of nasal infections in bony fish and the progress that has been made towards understanding how fish respond locally and systemically to nasal infection or vaccination. We also want to highlight the complex interactions between neurons and immune cells that occur in the olfactory organ during the course of an immune response. We predict that similar neuroimmune interactions govern immune responses at all mucosal tissues in bony fish. Understanding the principles of mucosal immune responses in teleost NALT has therefore revealed important aspects of fish mucosal immunity that are critical for mucosal vaccination in aquaculture.

Generation of Th17 cells in response to intranasal infection requires TGF-ß1 from dendritic cells and IL-6 from CD301b+ dendritic cells.

Intranasal (i.n.) infections preferentially generate Th17 cells. We explored the basis for this anatomic preference by tracking polyclonal CD4(+) T cells specific for an MHC class II-bound peptide from the mucosal pathogen Streptococcus pyogenes. S. pyogenes MHC class II-bound peptide-specific CD4(+) T cells were first activated in the cervical lymph nodes following i.n. inoculation and then differentiated into Th17 cells. S. pyogenes-induced Th17 formation depended on TGF-ß1 from dendritic cells and IL-6 from a CD301b(+) dendritic cell subset located in the cervical lymph nodes but not the spleen. Thus, the tendency of i.n. infection to induce Th17 cells is related to cytokine production by specialized dendritic cells that drain this site.

[The distribution of interleukins and cytokines in the mucous membranes of the nose and the nasopharynx in the patients presenting with the post-nasal drip syndrome]. / Raspredelenie interleikinov i tsitokinov v slizistoi obolochke nosa i nosoglotki pri izolirovannom sindrome postnazal'nogo zatekaniia.

The objective of the present study was to elucidate the distribution of interleukins and cytokines in the mucous membranes of the nose and the nasopharynx in the patients presenting with the post-nasal drip syndrome. The study included 20 patients with this pathological condition and 20 volunteers who comprised the control group. The samples of the mucous membranes of the nose and the nasopharynx were examined with the use of the immunohistochemical methods to identify the protein gene product 9.5, interleukin-6, interleukin-10, the tumour necrosis factor-alpha, nuclear factor-kB, and beta-defensin. It was shown that the post-nasal drip syndrome is characterized by the enhanced content of the protein gene product 9.5, interleukin-6, interleukin-10, the tumour necrosis factor-alpha, nuclear factor-kB, and beta-defensin in the mucous membranes of the nose and the nasopharynx.

Total nasal resistance among Sasang constitutional types: a population-based study in Korea.

BACKGROUND: There have been many attempts to find an objective phenotype by Sasang constitutional types (SCTs) on an anatomical, physiological, and psychological basis, but there has been no research on total nasal resistance (TNR) among SCTs. METHODS: We assessed the value of the TNR in the SCTs classified by an integrated diagnostic model. Included in the study were 1,346 individuals (701 males, 645 females) who participated in the Korean Genome and Epidemiology Study (KoGES). The TNR was measured by active anterior rhinomanometry (AAR) at transnasal pressures of 100 and 150 Pascal (Pa). RESULTS: The average TNR was 0.186 ± 0.004 Pa/cm3/second at 100 Pa in the Tae-eum (TE), 0.193 ± 0.007 in the So-eum (SE), and 0.208 ± 0.005 in the So-yang (SY) types. Under condition of 150 Pa the TE type had a TNR value of 0.217 ± 0.004, the SE type was 0.230 ± 0.008, and the SY type was 0.243 ± 0.005. Higher values of TNR were more likely to be reported in the SY type at 100 Pa and 150 Pa. In the stratified analysis by sex, the SY type in males and females tended to have higher TNR value than the TE and SE types at transnasal pressure of both 100 Pa and 150 Pa. CONCLUSIONS: These results provide new approaches to understand the functional characteristics among the SCTs in terms of nasal physiology. Further studies are required to clarify contributing factors for such a difference.

[Expression and significance of IgG4 in inflammatory disease of nasal cavity and paranasal sinuses].

OBJECTIVE: To study the prevalence of IgG4-positive plasma cells in inflammatory disease of nasal cavity and paranasal sinuses and its association with IgG4-related sclerosing disease (IgG4-SD). METHODS: The expression of IgG4 and IgG in plasma cells of 103 cases diagnosed as inflammatory disease of nasal cavity and paranasal sinuses with dense lymphoplasmacytic infiltrate was studied by immunohistochemistry (EnVision) and quantitatively analyzed by medical image analysis system. RESULTS: Immunohistochemical study showed marked infiltration by IgG4-positive plasma cells (>50 per high-power field) in 28 cases, moderate infiltration (30 to 50 per high-power field) in 23 cases, mild (10 to 29 per high-power field) in 30 cases and negative (<10 per high-power field) in 22 cases (P < 0.05). Twenty-two cases studied fulfilled the diagnostic criteria of IgG4-SD (>50 IgG4-positive plasma cells per high-power field and IgG4-to-IgG ratio > 40%), including 3 cases of chronic sinusitis (3/20), 3 cases of nasal polyps (3/18), 3 cases of inflammatory pseudotumor (3/17), 4 cases of fungal sinusitis (4/20), 1 case of rhinoscleroma (1/12), 7 cases of Wegener's granulomatosis (7/11) and 1 case of Rosai-Dorfman disease (1/2). CONCLUSION: Inflammatory disease of nasal cavity and paranasal sinuses fulfilling the diagnostic criteria IgG4-SD is not uncommon. Definitive diagnosis of IgG4-SD requires correlation with other clinical and laboratory findings. Some cases of unexplained inflammatory disease of nasal cavity and paranasal sinus may represent a member of the IgG4-SD spectrum. IgG4 carries diagnostic value in differential diagnosis of inflammatory disease occurring in nasal cavity and paranasal sinuses.

Central Retinal Artery Occlusion in Rhino-Orbital-Cerebral Mucormycosis: An Inflammatory-Prothrombotic State.

PURPOSE: The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019. DESIGN: A nonrandomized retrospective case-control study. METHODS: The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors. RESULTS: A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group. CONCLUSIONS: Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.

Sheep and goat immune responses to nose bot infestation: a review.

Oestrus ovis L. (Diptera: Oestridae) is a cosmopolitan agent of myiasis in sheep and goats. The parasitic phase begins after adult females deposit first-stage larvae (L1) into the nostrils of hosts; these larvae develop into L2 and L3 in the nasal and sinus horn cavities. Sneezing and nasal discharges are the major clinical signs in infected animals. The pathogenesis of O. ovis infection is caused by: (a) the trauma resulting from the mechanical action of spines and hooks during larval movement on mucosal membranes, and, more importantly, (b) an allergenic reaction provoked by molecules excreted/secreted by larvae, of which salivary antigens are those mainly recognized by the host's immune system. The recruitment of immune reactive cells increases gradually from the nasal to sinus cavities in infected hosts. Mast cells, eosinophils, macrophages and lymphocytes are always more numerous in infected than non-infected animals. Humoral (antibody) systemic response of immunoglobulin G (IgG) usually reaches seroconversion 2-4 weeks post-first infection and the highest levels are observed during the development of L2 and L3 larvae. Local antibody responses include specific IgG, which has been found to negatively correlate with larval survival and development. Hypersensitivity reaction, immunomodulation, immunization trials and mixed infections of O. ovis and helminths are discussed.

[Changes of immunological status in children presenting with recurrent nasal furuncles].

The authors present the original observations of the occurrence of nasal furuncles in the children residing in Moscow. They investigated the lymphocyte subpopulation composition and the content of the main classes of immunoglobulins in the peripheral blood of the children with clinical manifestations of recurrent nasal furuncles. It was shown that functional disturbances of the immune system in the children suffering recurring nasal furuncles affect both its cellular and humoral components, i.e. T-helpers and B-lymphocytes/immunoglobulin synthesis respectively.

Rhinocerebral mucormycosis secondary to severe acute pancreatitis and diabetic ketoacidosis: a case report.

INTRODUCTION: Rhinocerebral mucormycosis is a rare and severe form of opportunistic fungal infection that can develop rapidly and cause significant mortality, particularly among diabetic patients suffering from ketoacidosis. Diagnosing rhinocerebral mucormycosis during the early stages of infection is challenging. CASE PRESENTATION: We describe a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis. In this case, the condition was not diagnosed during the optimal treatment window. we therefore provide a thorough overview of related clinical findings and histopathological characteristics, and we discuss potential differential diagnoses. CONCLUSIONS: In summary, we described a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis, with the optimal treatment window for this condition having been missed. This report suggests that a definitive mucormycosis diagnosis can be made based upon tissue biopsy that reveals the presence of characteristic hyphae. Early diagnosis and treatment are essential in order to improve patient prognosis.

Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review.

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.

The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna Challenge Chamber.

OBJECTIVE AND DESIGN: This double-blind cross-over study compared the potential of bilastine, cetirizine, and fexofenadine to relieve the symptoms of allergic rhinitis. SUBJECTS AND METHODS: Seventy-five allergic volunteers were challenged with grass pollen in the Vienna Challenge Chamber (VCC) on two consecutive days of allergen provocation; 6 h on day 1 and 4 h day 2. Bilastine 20 mg, cetirizine 10 mg, fexofenadine 120 mg, or placebo were taken orally 2 h after the start of provocation on day 1 only. Total nasal symptom scores, the global symptom scores, nasal secretions, and eye symptoms were assessed on both day 1 and day 2. RESULTS AND CONCLUSIONS: Bilastine had a rapid onset of action, within 1 h, and a long duration of action, greater than 26 h. Cetirizine was similar. Fexofenadine was similar on day 1 but less effective on day 2, indicating a shorter duration of action. Bilastine, like cetirizine and fexofenadine, was safe and well tolerated in this study.

Comparative models for human nasal infections and immunity.

The human olfactory system is a mucosal surface and a major portal of entry for respiratory and neurotropic pathogens into the body. Understanding how the human nasopharynx-associated lymphoid tissue (NALT) halts the progression of pathogens into the lower respiratory tract or the central nervous system is key for developing effective cures. Although traditionally mice have been used as the gold-standard model for the study of human nasal diseases, mouse models present important caveats due to major anatomical and functional differences of the human and murine olfactory system and NALT. We summarize the NALT anatomy of different animal groups that have thus far been used to study host-pathogen interactions at the olfactory mucosa and to test nasal vaccines. The goal of this review is to highlight the strengths and limitations of each animal model of nasal immunity and to identify the areas of research that require further investigation to advance human health.

Rhinocerebral mucormycosis in an adolescent with type 1 diabetes mellitus: case report.

Rhinocerebral mucormycosis is a severe opportunistic infection affecting immunocompromised patients. A 14-year-old boy with rhino-orbito-cerebral mucormycosis and type 1 diabetes is described. He responded well to amphotericin B lipid complex followed by itraconazole.

Limiting Dietary Sugar Improves Pediatric Sinonasal Symptoms and Reduces Inflammation.

Excessive sugar consumption is associated with many chronic inflammatory diseases in adults. The effects of excessive sugar consumption in children have not been determined. In this study, we hypothesized that sinonasal symptoms and proinflammatory cytokine levels would be related and could be altered through reduction in sugar-sweetened beverage (SSB) consumption. To test this, we conducted a pilot study involving behavior modification and a 2-week follow-up. Seventeen children participants were recruited, and eleven completed the study. The experimental group presented with chronic nasal congestion or rhinorrhea defined by daily symptoms without acute illness for at least 3 months. The control group presented for non-nasal problems. Both groups received counseling to decrease SSB consumption. The Sinus and Nasal Quality of Life (SN-5) Survey was administered, and a blood sample was obtained by venipuncture at baseline and 2 weeks after counseling. Participants kept a 2-week food diary to document sugar intake. Serum lipid profile and inflammatory cytokines were measured. The experimental group reduced daily sugar intake, 46% versus 11% in the control. Baseline SN-5 scores were significantly worse in the experimental group and normalized to controls after intervention. Inflammatory cytokine levels were not different at baseline, but the experimental group significantly reduced in proinflammatory markers and increased the levels of anti-inflammatory markers after intervention. Our pilot data demonstrate higher sugar consumption may be associated with increased inflammatory stress and sinonasal symptoms. Reducing SSB and controlling inflammation in early childhood may have future health benefits.

[Progress of sino-nasal IgG4-related disease].

IgG4-related disease is a newly recognized systemic fibro inflammatory disorder that affects the sino-nasal region. It is a rare and emerging entity that can present with bony and soft-tissue invasion,the final diagnosis of this disease mainly depends on pathological examination and majority of patients receiving corticosteroids responded very well to treatment. Thus,Our goal was to highlight the sino-nasal presentation of this unique disease and to review previously reported cases from 2010 to 2016.We hope that clinical physicians to enhance understanding of the disease in order to ensure early diagnosis and early intervention to prevent serious injury and fibrosis of organs.

A prospective study of upper aerodigestive tract manifestations of mucous membrane pemphigoid.

We conducted a prospective study between 1995 and 2002 to investigate nose and throat (NT) manifestations of mucous membrane pemphigoid (MMP). One hundred ten consecutive patients with clinical, histologic, and immunologic criteria of MMP were seen in 2 referral centers for bullous diseases. They were systematically asked about the existence of persistent NT symptoms. Patients who had any were examined with a flexible nasopharyngolaryngoscope by the same otorhinolaryngologist. When possible, NT mucous membrane (MM) biopsies were taken for direct immunofluorescence (IF) assays to determine lesion specificity. Thirty-eight (35%) patients (23 F/15 M; mean age, 58.5 yr) had the following NT symptoms: 35 (92%) nasal, 19 (50%) pharyngeal, and 10 (26%) laryngeal. Five (13%) had acute dyspnea. Thirty-three (87%) of the 38 symptomatic patients had lesions at physical examination: 30 (79%) nasal, 6 (16%) pharyngeal, and 19 (50%) laryngeal. Laryngeal involvement was asymptomatic in 11 patients. Lesions were mainly atrophic rhinitis and oropharyngeal and epiglottal erosions. Nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 (18%) patients, causing the death of 3. Direct IF showed malpighian epithelium associated with linear immune deposits (IgG, IgA, or C3) along the chorioepithelial junction in all 18 biopsies performed, including those of 4 symptomatic patients without lesions at physical examination. The presence of severe ophthalmologic lesions (p = 0.02) and > or =3 sites involved other than NT (p = 0.02) were predictive of laryngeal involvement. In contrast, laryngeal symptoms, disease duration, HLA DQB1*0301, and smoking were not significantly associated with laryngeal lesions. In conclusion, at least 35% of MMP patients had NT involvement. Atrophic rhinitis was the most frequent lesion. The most severe were the laryngeal lesions that were significantly associated with severe ocular involvement and disseminated disease, and could be fatal. Our results highlight the necessity of a multidisciplinary approach to MMP management to assure early diagnosis of NT involvement, to guide therapeutic choices, and to improve patient survival and functional outcomes.

Sino-nasal bony and cartilaginous destruction associated with cocaine abuse, S. aureus and antineutrophil cytoplasmic antibodies.

Three male patients aged 29, 30 and 34 years and a 36-year-old female are reported with nasal septum perforation and a history of cocaine abuse. Two of the patients also had a perforation of the hard palate. In all four, antineutrophil cytoplasmic antibodies (ANCA) were found. One had a cytoplasmic immunofluorescence-staining pattern (c-ANCA), the other three showed a perinuclear staining pattern (p-ANCA). Furthermore, all patients were found to be nasal carriers of S. aureus. We hypothesise that tissue damage to the nasal and palatal area in patients using cocaine may partly be mediated by the presence of ANCA antibodies. Furthermore, we speculate that S. aureus facilitates the development of these ANCA antibodies.