RESUMEN
C-type lectin receptors (CLRs) comprise a large family of immunoreceptors that recognize polysaccharide ligands exposed on pathogen surfaces and are conserved among mammals. However, interspecies differences in their ligand spectrums are not fully understood. Dectin-1 is a well-characterized CLR that recognizes ß-glucan. We report here that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dectin-1. Low-valency ß-glucan components within fucan appeared to be responsible for this activation, as the ligand activity was eliminated by ß-glucanase treatment. The low-valency ß-glucan laminarin also acted as an agonist for human Dectin-1 but not for mouse Dectin-1, whereas the high-valency ß-glucan curdlan activated both human and mouse Dectin-1. Reciprocal mutagenesis analysis revealed that the ligand-binding domain of human Dectin-1 does not determine its unique sensitivity to low-valency ß-glucan. Rather, we found that its intracellular domain renders human Dectin-1 reactive to low-valency ß-glucan ligand. Substitution with two amino acids, Glu2 and Pro5, located in the human Dectin-1 intracellular domain was sufficient to confer sensitivity to low-valency ß-glucan in mouse Dectin-1. Conversely, the introduction of mouse-specific amino acids, Lys2 and Ser5, to human Dectin-1 reduced the reactivity to low-valency ß-glucan. Indeed, low-valency ligands induced a set of proinflammatory genes in human but not mouse dendritic cells. These results suggest that the intracellular domain, not ligand-binding domain, of Dectin-1 determines the species-specific ligand profile.
Asunto(s)
Glucanos/metabolismo , Lectinas Tipo C/metabolismo , Polisacáridos/metabolismo , beta-Glucanos/metabolismo , Sustitución de Aminoácidos , Animales , Línea Celular , Humanos , Lectinas Tipo C/genética , Ratones , Mutagénesis , Mutación Missense , Dominios Proteicos , Especificidad de la Especie , Especificidad por Sustrato/fisiologíaRESUMEN
Among various innate immune receptor families, the role of C-type lectin receptors (CLRs) in lung protective immunity against Streptococcus pneumoniae (S. pneumoniae) is not fully defined. We here show that Mincle gene expression was induced in alveolar macrophages and neutrophils in bronchoalveolar lavage fluids of mice and patients with pneumococcal pneumonia. Moreover, S. pneumoniae directly triggered Mincle reporter cell activation in vitro via its glycolipid glucosyl-diacylglycerol (Glc-DAG), which was identified as the ligand recognized by Mincle. Purified Glc-DAG triggered Mincle reporter cell activation and stimulated inflammatory cytokine release by human alveolar macrophages and alveolar macrophages from WT but not Mincle KO mice. Mincle deficiency led to increased bacterial loads and decreased survival together with strongly dysregulated cytokine responses in mice challenged with focal pneumonia inducing S. pneumoniae, all of which was normalized in Mincle KO mice reconstituted with a WT hematopoietic system. In conclusion, the Mincle-Glc-DAG axis is a hitherto unrecognized element of lung protective immunity against focal pneumonia induced by S. pneumoniae.
Asunto(s)
Glucolípidos/metabolismo , Lectinas Tipo C/inmunología , Macrófagos Alveolares/inmunología , Neumonía Neumocócica/inmunología , Receptores Inmunológicos/inmunología , Streptococcus pneumoniae/inmunología , Animales , Cromatografía Líquida de Alta Presión , Citometría de Flujo , Glucolípidos/inmunología , Humanos , Inmunofenotipificación , Lectinas Tipo C/metabolismo , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Inmunológicos/metabolismo , Streptococcus pneumoniae/metabolismoRESUMEN
Nodal T-follicular helper cell lymphoma (nTFHL), a hematologic neoplasm originating from T-follicular helper (TFH) cells, occasionally presents with pulmonary radiographic abnormalities, without neoplastic cellular infiltration. However, the precise mechanisms underlying non-neoplastic pulmonary opacities in patients with nTFHL remain unclear. Previous reports have shown that TFH cell abnormalities are associated with collagen disease and interstitial pneumonia with autoimmune features (IPAF). We herein report a patient with nTFHL accompanied by interstitial pneumonia diagnosed via lung and lymph node biopsies. These findings suggest the need to rule out nTFHL before diagnosing IPAF.
RESUMEN
Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease characterized by the accumulation of alveolar surfactants due to dysfunction of granulocyte-macrophage colony-stimulating factor-dependent cholesterol clearance. Whole-lung lavage is the current standard of care for PAP, but it can lead to the exacerbation of hypoxia. A medication targeting cholesterol homeostasis is a promising therapy for refractory PAP. We present a case of autoimmune PAP with severe hypoxia that was successfully treated with segmental lung lavage (SLL). Following SLL for disease relapse, statin treatment for dyslipidemia was started. After initiating statin treatment, the patient did not require bronchoalveolar lavage for 10 months.
RESUMEN
Chronic eosinophilic pneumonia (CEP) is a rare disorder characterized by marked accumulation of eosinophils in lung tissues and/or bronchoalveolar lavage fluid (BALF). Patients with CEP usually respond well to corticosteroids. However, more than half of these patients relapse while tapering and/or after discontinuing corticosteroids. Long-term adverse effects of corticosteroids can be serious. We report a case of comorbid CEP, severe bronchial asthma, eosinophilic bronchiolitis, and chronic airway infection. Corticosteroid treatment induced remission of the CEP, but recurrent exacerbation of the chronic airway infection occurred. Thus, she was treated with benralizumab, a monoclonal antibody against the alpha-chain of interleukin-5 receptor. After the initiation of benralizumab, the steroid was stopped successfully and her CEP, asthma, and airway infection remained well controlled. Micronodular nodules on high-resolution computed tomography (HRCT) reflecting bronchiolitis were also improved with benralizumab treatment. Benralizumab may be a treatment option for patients not tolerating steroids.
RESUMEN
OBJECTIVES: The purpose of this clinical study was to examine the relationships of v-shaped noncarious cervical lesion (NCCL) formation with occlusal factors. METHODS: A total of 159 male self-defense force officials with a mean age of 36.2 years participated in this study. All present teeth were examined for the presence and type of NCCL using the Tooth Wear Index (TWI). The subjects were then interviewed about bruxing and toothbrushing habit. Finally, occlusal force, occlusal contact area and average pressure were measured using a pressure-detecting sheet. Subject-level logistic regression was carried out to assess the associations of factors with presence of v-shaped NCCL teeth. Subjects without v-shaped NCCL were designated as control subjects. RESULTS: Totally, 4518 teeth were examined. Seventy-eight subjects (49.1%) had one or more teeth with typical v-shaped NCCL (259 teeth). The number of teeth with v-shaped NCCL of grade 2 (defect less than 1mm in depth) was 195 (4.3%), and the number of teeth with v-shaped NCCL of grade 3 (defect 1-2mm in depth) was 54 (1.2%). The prevalence of teeth with v-shaped NCCL was significantly higher in the maxilla than in the mandible. Most of the NCCL teeth were premolars. There was no significant difference between teeth with NCCL on the right side and those on the left side. Subject-level logistic regression analysis revealed that age (OR=1.11), toothbrushing pressure (400g, OR=2.43) and occlusal contact area (>23.0mm(2), OR=4.15) were associated with the presence of NCCL teeth. CONCLUSIONS: It is concluded that aging, toothbrushing pressure and occlusal contact area are associated with the presence of NCCLs.
Asunto(s)
Fuerza de la Mordida , Bruxismo/complicaciones , Oclusión Dental Traumática/complicaciones , Cuello del Diente/patología , Erosión de los Dientes/etiología , Adulto , Estudios Transversales , Esmalte Dental/patología , Lateralidad Funcional , Humanos , Registro de la Relación Maxilomandibular , Modelos Logísticos , Masculino , Mandíbula , Maxilar , Abrasión de los Dientes/clasificación , Abrasión de los Dientes/etiología , Abrasión de los Dientes/patología , Erosión de los Dientes/clasificación , Erosión de los Dientes/patología , Cepillado Dental/efectos adversos , Adulto JovenRESUMEN
Crizotinib was the first clinically available inhibitor of the tyrosine kinase ALK, and next-generation ALK inhibitors, such as alectinib, are now under development. Although crizotinib is generally well tolerated, severe esophageal injury has been reported as a rare but serious adverse event of crizotinib therapy. We now describe the successful treatment with alectinib of a patient who developed crizotinib-induced esophageal ulceration.