Innate Immunity to<i>Aspergillus</i>Species

Park, Stacy J.; Mehrad, Borna

doi:10.1128/cmr.00014-09

Cited by 190 publications

(165 citation statements)

References 182 publications

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“…The initially inhaled resting conidia (RC) convert to swollen conidia (SC) within 4-5 h upon arrival in the lungs and germinate to form germ tubes and, later, hyphae (18). Proteomic approaches revealed differences in the most abundant proteins present in conidia and hyphae (19)(20)(21).…”

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confidence: 99%

Identification of Immunogenic Antigens from Aspergillus fumigatus by Direct Multiparameter Characterization of Specific Conventional and Regulatory CD4+ T Cells

Bächer

Kniemeyer

Teutschbein

et al. 2014

The Journal of Immunology

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CD4+ T cells orchestrate immune responses against fungi, such as Aspergillus fumigatus, a major fungal pathogen in humans. The complexity of the fungal genome and lifestyle questions the existence of one or a few immune-dominant Ags and complicates systematic screening for immunogenic Ags useful for immunotherapy or diagnostics. In this study, we used a recently developed flow cytometric assay for the direct ex vivo characterization of A. fumigatus–specific CD4+ T cells for rapid identification of physiological T cell targets in healthy donors. We show that the T cell response is primarily directed against metabolically active A. fumigatus morphotypes and is stronger against membrane protein fractions compared with cell wall or cytosolic proteins. Further analysis of 15 selected single A. fumigatus proteins revealed a highly diverse reactivity pattern that was donor and protein dependent. Importantly, the parallel assessment of T cell frequency, phenotype, and function allowed us to differentiate between proteins that elicit strong memory T cell responses in vivo versus Ags that induce T cell exhaustion or no reactivity in vivo. The regulatory T cell (Treg) response mirrors the conventional T cell response in terms of numbers and target specificity. Thus, our data reveal that the fungal T cell immunome is complex, but the ex vivo characterization of reactive T cells allows us to classify Ags and to predict potential immunogenic targets. A. fumigatus–specific conventional T cell responses are counterbalanced by a strong Treg response, suggesting that Treg-depletion strategies may be helpful in improving antifungal immunity.

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confidence: 99%

Identification of Immunogenic Antigens from Aspergillus fumigatus by Direct Multiparameter Characterization of Specific Conventional and Regulatory CD4+ T Cells

Bächer

Kniemeyer

Teutschbein

et al. 2014

The Journal of Immunology

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“…Chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA) occur in immunocompetent hosts (3)(4)(5)(6)(7)(8)(9). CPA usually affects patients with underlying lung disease, such as mycobacterial infections, chronic obstructive pulmonary disease (COPD), ABPA, and emphysema (7,9,10).…”

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confidence: 99%

Prospective Evaluation of a New Aspergillus IgG Enzyme Immunoassay Kit for Diagnosis of Chronic and Allergic Pulmonary Aspergillosis

et al. 2016

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j Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial enzyme immunoassay (EIA) (Bordier Affinity Products) with that of the Bio-Rad and Virion‫گ‬Serion EIAs. This assay is novel in its association of two recombinant antigens with somatic and metabolic antigens of Aspergillus fumigatus. In a prospective multicenter study, 436 serum samples from 147 patients diagnosed with CPA (136 samples/104 patients) or ABPA (94 samples/43 patients) and from 205 controls (206 samples) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad, and Virion‫گ‬Serion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (P < 0.01), which was itself more sensitive than the Virion‫گ‬Serion kit (P ‫؍‬ 0.04). The Bordier and Bio-Rad kits had similar specificity (P ‫؍‬ 0.8), both higher than that of the Virion‫گ‬Serion kit (P ‫؍‬ 0.02). The area under the receiver operating characteristic (ROC) curves confirmed the superiority of the Bordier kit over the Bio-Rad and the Virion‫گ‬Serion kits (0.977, 0.951, and 0.897, respectively; P < 0.01 for each comparison). In a subset analysis of 279 serum samples tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; P ‫؍‬ 0.10). The use of recombinant, somatic, and metabolic antigens in a single EIA improved the balance of sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis.

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“…pulmonary infe ears and is asso [27,28] . The i hematopoietic of aggressive ch seases such as sis, neoplasm w mmune compro connective tis e-binding lecti aracterized by n ence of hyphae other organs ar der individuals oss that occurs ients may be as d by chronic ca ent pleural thic [22] .…”

Section: Pa)mentioning

confidence: 99%

An update of clinical characteristics and imaging findings of pulmonary aspergillosis

Sah

Liu

Ganganah

et al. 2015

IJDI

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Pulmonary aspergillosis (PA) is a clinical spectrum of rapidly progressive potentially fatal opportunistic mycosis usually caused by Aspergillus organisms. In the recent years, the number of patients with invasive pulmonary aspergillosis (IPA) has increased and it remains a major cause of morbidity and mortality in immunocompromised patients. Chest CT plays an important role in the early diagnosis of IPA and should be included in the investigative protocol. Typical imaging findings of IPA include nodule, consolidation, the halo sign, the hypodense sign and the air crescent sign. CT Angiography (CTA) has a higher sensitivity for detecting angioinvasive aspergillosis. However, the diagnosis of pulmonary aspergillosis remains challenging radiologically in immunocompetent chronic obstructive pulmonary disease (COPD) and critically ill patients in intensive care unit (ICU) because of the non-specific CT findings and further studies are needed to establish the confirm diagnosis.

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Innate Immunity toAspergillusSpecies

Cited by 190 publications

References 182 publications

Identification of Immunogenic Antigens from Aspergillus fumigatus by Direct Multiparameter Characterization of Specific Conventional and Regulatory CD4+ T Cells

Identification of Immunogenic Antigens from Aspergillus fumigatus by Direct Multiparameter Characterization of Specific Conventional and Regulatory CD4+ T Cells

Prospective Evaluation of a New Aspergillus IgG Enzyme Immunoassay Kit for Diagnosis of Chronic and Allergic Pulmonary Aspergillosis

An update of clinical characteristics and imaging findings of pulmonary aspergillosis

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