Induction of innate immunity by Aspergillus fumigatus cell wall polysaccharides is enhanced by the composite presentation of chitin and beta-glucan

Chitin and β-glucan are conserved throughout evolution in the fungal cell wall and are the most common polysaccharides in fungal species. Together, these two polysaccharides form a structural scaffold that is essential for the survival of the fungus. In the present study, we demonstrated that Aspergillus fumigatus alkali-insoluble cell wall fragments (AIF), composed of chitin linked covalently to β-glucan, induced enhanced immune responses when compared with individual cell wall polysaccharides. Intranasal administration of AIF induced eosinophil and neutrophil recruitment, chitinase activity, TNF-α and TSLP production in mice lungs. Selective destruction of chitin or β-glucan from AIF significantly reduced eosinophil and neutrophil recruitment as well as chitinase activity and cytokine expression by macrophages, indicating the synergistic effect of the cell wall polysaccharides when presented together as a composite PAMP. We also showed that these cell wall polysaccharides induced chitin-specific IgM in mouse serum. Our in vivo and in vitro data indicate that chitin and β-glucan play important roles in activating innate immunity when presented as composite cell wall PAMPs.     

Pituitary aspergillus infection

Fungal infection should be considered in the differential diagnosis of a pituitary or sellar mass, albeit fungal infections involving the pituitary gland and sella are a rare occurrence. We report a case of Aspergillus infection involving the pituitary gland and sellar region discovered in a 74-year-old man. The patient had a history of hypertension, chronic renal disease, autoimmune hemolytic anemia and presented with right eye pain, headaches and worsening hemiparesis. Imaging studies revealed a right internal carotid artery occlusion and an acute right pontine stroke along with smaller infarcts in the right middle cerebral artery distribution. Clinically, the patient was thought to have vasculitis. An infectious etiology was not identified. He developed respiratory distress and died. At autopsy, necrotizing meningitis was discovered. A predominantly chronic inflammatory cell infiltrate consisting of benign-appearing lymphocytes, plasma cells and macrophages was accompanied by acute angle branching, angioinvasive hyphae which were highlighted on Gomori methenamine silver staining and were morphologically consistent with Aspergillus species. In previously reported cases of Aspergillus infection involving the pituitary or sella, most presented with headaches or impaired vision and were not immunocompromised. A transsphenoidal surgical approach is recommended in suspected cases in order to minimize the risk of dissemination of the infection. Some patients have responded well to antifungal medications once diagnosed.     

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Eosinophilic pneumonia was confirmed by bronchoalveolar lavage fluid examination and transbronchial lung biopsy. Aspergillus niger was cultured from the patient's pharyngeal swab and bronchoalveolar lavage fluid. Inhalation bronchoprovocation test with A. niger antigen was positive. Although the patient's condition improved promptly with 10 mg/day prednisolone administration, dry cough recurred approximately 2 months after completion of this therapy. Severe coughing disappeared on oral cleansing with 300 mg/day amphotericin B, and he recovered completely on 100 mg/day amphotericin B administration. Oral cleansing with amphotericin B may be efficacious in preventing relapses of eosinophilic pneumonia caused by allergic reaction to fungal antigen.     

Genetic susceptibility to infections with Aspergillus fumigatus

Infections with the opportunistic mold Aspergillus fumigatus show high morbidity and mortality. Risk factors for the development of invasive aspergillosis are neutropenia, T-cell depletion, CD34-selected stem cell products, corticosteroid therapy, and cytomegalovirus infections.

Recently, a growing number of defined single nucleotide polymorphisms have been described that genetically determine susceptibility to A. fumigatus. This includes genes encoding for cytokines or chemokines and their receptors, toll-like receptor genes, and other genes involved in innate immunity.

This review summarizes the current knowledge about the growing number of genetic markers and their relevance for the course and outcome of infections with A. fumigatus.     

Mycotic Otitis Media in a Harbour Porpoise (Phocoena phocoena)

A 9-year-old by-caught harbour porpoise (Phocoena phocoena) was subject to routine post-mortem examination. Major findings included parasitic infection (Stenurus minor) of the left middle ear and severe mycotic infection of the right middle ear. The morphological appearance of the causative organism was consistent with Aspergillus fumigatus. These pathological findings were likely to have impaired echolocation in this animal and this may have contributed to the by-catch. The ears of marine mammals should be examined routinely during post-mortem investigations.     

Opportunistic Aspergillus pathogens measured in home and hospital tap water by quantitative PCR (QPCR)

Opportunistic fungal pathogens are a concern because of the increasing number of immunocompromised patients. The goal of this research was to test a simple extraction method and rapid quantitative PCR (QPCR) measurement of the occurrence of potential pathogens, Aspergillus fumigatus, A. flavus, A. terreus and A. niger, in home tap water and a hospital water supply.     

Effect of different sample volumes on the DNA extraction of Aspergillus fumigatus from whole blood

Five methods were compared, using conventional PCR, for the isolation of DNA from Aspergillus fumigatus conidia from 1–3-mL samples of whole blood. A lower detection threshold of Aspergillus conidia was achieved using 3-mL rather than 1-mL samples with three of five methods tested.     

肺部曲霉菌属感染的临床与耐药性研究

目的检测6种常用抗真菌药物对曲霉菌属的体外抗菌活性,探讨肺部曲霉菌属感染的相关因素与预后。方法采用Etest法测定伊曲康唑、酮康唑、5-氟胞嘧啶、卡泊芬净、两性霉素B和氟康唑对18株曲霉的最低抑菌浓度(MIC);用回顾性调查的方法对肺部曲霉菌属感染患者进行分析。结果卡泊芬净、伊曲康唑、两性霉素B对曲霉菌属的MIC90分别为0.25、1.0、2.0μg/ml,酮康唑、5-氟胞嘧啶和氟康唑的MIC90分别≥32、32、256μg/ml;卡泊芬净对各种曲霉菌属的抑菌效果均较好;伊曲康唑对烟曲霉、黄曲霉的体外抗菌活性高于两性霉素B,两性霉素B对黑曲霉的体外抗菌活性高于伊曲康唑;大多肺部曲霉菌属感染患者有高龄、基础疾病等。结论高龄、基础疾病、广谱抗菌药物使用是曲霉菌属感染的主要原因,肺部曲霉菌属感染病死率高;伊曲康唑、卡泊芬净和两性霉素B对曲霉菌属的体外抑菌效果较好,但不同药物对不同种类曲霉菌属抗菌活性不同,实验室将曲菌鉴定到种并进行体外抗真菌药敏感试验对临床具有重要的指导意义。