- Helper T-Cell Responses and Pulmonary Fungal Infections. [Review]
- IImmunology 2018 May 20
- The mucosal surface of the respiratory tract encounters microbes, such as fungal particles, with every inhaled breath. When pathogenic fungi breach the physical barrier and innate immune system withi...
The mucosal surface of the respiratory tract encounters microbes, such as fungal particles, with every inhaled breath. When pathogenic fungi breach the physical barrier and innate immune system within the lung to establish an infection, adaptive immunity is engaged often in the form of helper CD4 T-cell responses. Type 1 responses, characterized by IFNγ production from CD4 cells, promote clearance of Histoplasma capsulatum and Cryptococcus neoformans infection. Likewise, IL-17A production from Th17 cells promotes immunity to Blastomyces dermatitidis and Coccidiodes species infection by recruiting neutrophils. In contrast the development of Th2 responses, characterized by IL-5 production from T-cells and eosinophil influx into the lungs, drives allergic bronchopulmonary aspergillosis and poor outcomes during C. neoformans infection. Experimental vaccines against several endemic mycoses, including Histoplasma capsulatum, Coccidioides, Cryptococcus, and Blastomyces dermatitidis, induce protective T-cell responses and foreshadow the development vaccines against pulmonary fungal infections for use in humans. Additionally, recent work using antifungal T-cells as immunotherapy to protect immune compromised patients from opportunist fungal infections also shows great promise. This review covers the role of T-cell responses in driving protection and pathology in response to pulmonary fungal infections, and highlight promising therapeutic applications of antifungal T-cells. This article is protected by copyright. All rights reserved.
- CARD9S12N facilitates the production of IL-5 by alveolar macrophages for the induction of type 2 immune responses. [Journal Article]
- NINat Immunol 2018 May 18
- The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the TH1 and TH17 subsets of helper T cells. The single-nuc...
The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the TH1 and TH17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9S12N), is associated with several autoimmune diseases. However, the function of CARD9S12N has remained unknown. Here we generated CARD9S12N knock-in mice and found that CARD9S12N facilitated the induction of type 2 immune responses after engagement of CLRs. Mechanistically, CARD9S12N mediated CLR-induced activation of the non-canonical transcription factor NF-κB subunit RelB, which initiated production of the cytokine IL-5 in alveolar macrophages for the recruitment of eosinophils to drive TH2 cell-mediated allergic responses. We identified the homozygous CARD9 mutation encoding S12N in patients with allergic bronchopulmonary aspergillosis and revealed activation of RelB and production of IL-5 in peripheral blood mononuclear cells from these patients. Our study provides genetic and functional evidence demonstrating that CARD9S12N can turn alveolar macrophages into IL-5-producing cells and facilitates TH2 cell-mediated pathologic responses.
- Risk factors for lung disease progression in children with cystic fibrosis. [Journal Article]
- EREur Respir J 2018 May 17
- To identify potential risk factors for lung disease progression in children with cystic fibrosis (CF), we studied the longitudinal data of all children with CF (aged ≥5 years) registered in the Dutch...
To identify potential risk factors for lung disease progression in children with cystic fibrosis (CF), we studied the longitudinal data of all children with CF (aged ≥5 years) registered in the Dutch CF Registry (2009-2014). Lung disease progression was expressed as a decline in lung function (FEV1%pred) and the pulmonary exacerbation rate (PEx). Potential risk factors at baseline included: sex, age, best FEV1%pred, best forced vital capacity (FVC)%pred, genotype, BMI z-score, pancreatic insufficiency, medication use (proton pump inhibitors [PPI], prophylactic antibiotics, and inhaled corticosteroids), CF-related diabetes, allergic bronchopulmonary aspergillosis, and colonisation with Pseudomonas aeruginosaThe data of 545 children were analysed. PPI use was associated with both annual decline of FEV1%pred (p=0.017) and future PEx (p=0.006). Moreover, lower FEV1%pred at baseline (p=0.007), prophylactic inhaled antibiotics use (p=0.006), and PEx in the baseline year (p=0.002) were related to PEx in subsequent years.In a cohort of Dutch children with CF followed for five years, we were able to identify several risk factors for future exacerbations. Especially the association between PPI use and lung disease progression definitely requires further investigation.
- Concordance between Aspergillus-specific precipitating antibody and IgG in allergic bronchopulmonary aspergillosis. [Journal Article]
- AIAllergol Int 2018 May 15
- CONCLUSIONS: Positive rate of A. fumigatus-specific precipitin or IgG (ImmunoCAP) was superior to IgG (CF), but relatively poor concordance was noted between precipitin and IgG (ImmunoCAP). Positive precipitin for A. fumigatus suggests more active diseases. Cross-reactivity may exist between antibodies to different Aspergillus spp. Therefore, the type III hypersensitivity results in ABPA diagnosis should be carefully evaluated.
- Adrenal Insufficiency in Cystic Fibrosis: A Rare Phenomenon? [Journal Article]
- CRCan Respir J 2018; 2018:3629031
- CONCLUSIONS: This study is the first to systematically examine the presence of AI in the largest cohort of CF patients studied to date with a prevalence of 8%. Patients treated with corticosteroids and those colonized with Aspergillus have a greater risk of AI.
- Aspergillus precipitating antibody in patients with Mycobacterium avium complex lung disease: A cross-sectional study. [Journal Article]
- RMRespir Med 2018; 138:1-6
- CONCLUSIONS: APAb is associated with lower pulmonary function, and observed especially in patients with longer duration of MAC-LD and severe bronchiectasis, even in the absence of cavitary lesions.
- [Clinical Analysis of 40 Patients with Eosinophilic Lung Diseases in Peking Union Medical College Hospital]. [Journal Article]
- ZYZhongguo Yi Xue Ke Xue Yuan Xue Bao 2018 Apr 28; 40(2):170-177
- Objective To summarize the clinical features of eosinophilic lung diseases(ELD). Methods We retrospectively analyzed the clinical manifestations,laboratory findings,accessory examination results,and ...
Objective To summarize the clinical features of eosinophilic lung diseases(ELD). Methods We retrospectively analyzed the clinical manifestations,laboratory findings,accessory examination results,and pathology of 40 patients who were diagnosed with ELD and hospitalized in Peking Union Medical College Hospital from January 2013 to December 2016.Results There were 19 males and 21 females,and the average age was(48.58±18.25) years.The diagnoses included allergic bronchopulmonary aspergillosis(n=20),eosinophilic granulomatosis with polyangiitis(also known as churg-strauss syndrome)(n=10),chronic eosinophilic pneumonia(n=8),parasitic infection(n=1),and drug-induced eosinophilic pneumonia(n=1).Eosinophils counts in peripheral blood were increased in 35 patients(87.5%),and eosinophils counts in bronchoalveolar lavage fluids increased in 17 of 18 patients(94.4%).Arterial blood gas analysis showed varying degrees of hypoxemia in 23 patients(57.5%),and pulmonary function test showed ventilatory dysfunction in 27 patients(67.5%) and defect in diffusion capacity in 12 patients(30.0%).Chest CT revealed bilateral flaky,streaky,or diffuse ground-glass infiltrates and consolidations;in addition,central cylindrical bronchiectasis and mucous plugging with "finger-in-glove" pattern were seen in patients with allergic bronchopulmonary aspergillosis.Diffuse eosinophil infiltration was revealed in lung or other tissue biopsy.Glucocorticoids alone or combined with other therapies were effective in most patients.Conclusions ELD has a wide range of clinical presentations and can easily be misdiagnosed.Increased eosinophils count in peripheral blood and bronchoalveolar lavage fluids combined with infiltration manifestations in chest imaging are helpful for the diagnosis of ELD.Oral administration of glucocorticoids is the primary therapy for ELD.
- Burden of Serious Fungal Infections in Argentina. [Journal Article]
- JFJ Fungi (Basel) 2018 Apr 24; 4(2)
- The number of fungal infections at any given time in Argentina is not known. Here we estimate the burden of serious fungal infections in Argentina for the first time. Specific population statistics w...
The number of fungal infections at any given time in Argentina is not known. Here we estimate the burden of serious fungal infections in Argentina for the first time. Specific population statistics were searched from multiple sources, local literature was identified, and estimates made. Some additional data were sourced from the Ministry of Health, the Global Initiative for Asthma (GINA) program, and national haematology and transplant societies. Argentina has a population of 43.8 million, with 25% of this total being children under 15 years. The predicted candidemia annual incidence is 2193 cases, with 50% occurring in the ICU. At a 6% prevalence rate, an estimated 593,695 women suffer from recurrent vulvovaginal candidiasis. Invasive aspergillosis is relatively common because of high smoking and chronic obstructive pulmonary disease (COPD) rates, with 268 cases in immunocompromised patients and another 1938 in the 168,000 COPD patients admitted to hospital. Asthma is also common, affecting 14% of adults, and so allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) are major problems. An estimated 432 cases of cryptococcal meningitis (CM)-90% of them in AIDS patients-and 1177 cases of Pneumocystis pneumonia (PCP) occur each year. The estimated annual case number of disseminated histoplasmosis is 404 in AIDS patients, almost as frequent as CM. Paracoccidioidomycosis annual incidence is estimated at 219, and coccidioidomycosis at 16 cases. At least 881,023 people (>2.01%) in Argentina are affected by a serious fungal disease annually, with considerable morbidity and mortality.
- Clinical Characteristics of Fifty Patients with Allergic Bronchopulmonary Aspergillosis. [Journal Article]
- CMChin Med J (Engl) 2018 May 05; 131(9):1108-1109
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- Determination of an Aspergillus fumigatus-Specific Immunoglobulin G Reference Range in an Adult Omani Population. [Journal Article]
- SQSultan Qaboos Univ Med J 2018; 18(1):e43-e46
- CONCLUSIONS: The A. fumigatus-specific IgG reference range within a healthy adult Omani population was comparable to those reported in other populations.