Advances Against Aspergillosis: Biology, Host response, Diagnosis and Treatment

Askew, David; Kontoyiannis, Dimitrios P.; Clemons, Karl V.

doi:10.1007/s11046-014-9819-4

Mycopathologia

2014

DOI: 10.1007/s11046-014-9819-4

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Advances Against Aspergillosis: Biology, Host response, Diagnosis and Treatment

David Askew

Dimitrios P. Kontoyiannis

Karl V. Clemons

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Cited by 4 publications

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“…Hosts with immune hypersensitivity are predisposed to allergic aspergillosis and aspergilloma (7)(8)(9), whereas those with compromised immune status are susceptible to invasive aspergillosis (10). Immunocompetent individuals, however, are capable of efficiently eliminating the inhaled conidia by innate immune mechanisms (11)(12)(13). The last 2 decades have seen a significant increase in the invasive aspergillosis cases because of the widespread use of immunosuppressant drugs, particularly in hemato-oncology patients and transplant recipients (14 -17).…”

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Aspergillus fumigatus conidial metalloprotease Mep1p cleaves host complement proteins

Shende¹,

Wong

Rapole

et al. 2018

Journal of Biological Chemistry

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Innate immunity in animals including humans encompasses the complement system, which is considered an important host defense mechanism against , one of the most ubiquitous opportunistic human fungal pathogens. Previously, it has been shown that the alkaline protease Alp1p secreted from mycelia degrades the complement components C3, C4, and C5. However, it remains unclear how the fungal spores ( conidia) defend themselves against the activities of the complement system immediately after inhalation into the lung. Here, we show that conidia contain a metalloprotease Mep1p, which is released upon conidial contact with collagen and inactivates all three complement pathways. In particular, Mep1p efficiently inactivated the major complement components C3, C4, and C5 and their activation products (C3a, C4a, and C5a) as well as the pattern-recognition molecules MBL and ficolin-1, either by directly cleaving them or by cleaving them to a form that is further broken down by other proteases of the complement system. Moreover, incubation of Mep1p with human serum significantly inhibited the complement hemolytic activity and conidial opsonization by C3b and their subsequent phagocytosis by macrophages. Together, these results indicate that Mep1p associated with and released from conidia likely facilitates early immune evasion by disarming the complement defense in the human host.

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mentioning

confidence: 99%

Aspergillus fumigatus conidial metalloprotease Mep1p cleaves host complement proteins

Shende¹,

Wong

Rapole

et al. 2018

Journal of Biological Chemistry

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Coinfection of Pulmonary Hydatid Cyst and Aspergilloma: Case Report and Systematic Review

et al. 2015

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Aspergilloma infection consists of a mass of fungal hyphae, inflammatory cells, fibrin, mucus, and tissue debris and can colonize lung cavities due to underlying diseases such as tuberculosis, sarcoidosis, bronchiectasis, cavitary lung cancer, neoplasms, ankylosing spondylitis, bronchial cysts, and pulmonary infarction. Here we report coinfection of pulmonary hydatid cyst and aspergilloma in a 34-year-old female who had had history of minor thalassemia and suffered from chest pain, dyspnea, non-productive cough for at least five months, and hemoptysis for 20 days. Radiographic sign showed a large cavitary lesion (5 × 6 × 6 cm) involving left lower lobe (LLL). Dichotomous septate hyphae were observed in bronchoalveolar lavage and biopsy specimens from LLL. The patient subsequently improved after combined anti-helminth therapies with albendazole (400 mg/bd) and lobectomy. According to morphological and molecular characterization, Aspergillus niger was confirmed. In vitro antifungal susceptibility tests revealed that the MIC values for the antifungals used in this case in increasing order were posaconazole (0.125 µg/ml), itraconazole and voriconazole (0.5 µg/ml), and amphotericin B (1 µg/ml). The minimum effective concentration for caspofungin was 0.125 µg/ml. Subsequently, we systematically reviewed 22 confirmed cases of pulmonary hydatid cyst and aspergilloma during a period of 19 years (1995-2014) and discussed the epidemiology, clinical features, and treatment of this disease.

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Pulmonary Aspergillus Overlap Syndromes

Jiang

Shao

2017

Mycopathologia

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Advances Against Aspergillosis: Biology, Host response, Diagnosis and Treatment

Cited by 4 publications

References 31 publications

Aspergillus fumigatus conidial metalloprotease Mep1p cleaves host complement proteins

Aspergillus fumigatus conidial metalloprotease Mep1p cleaves host complement proteins

Coinfection of Pulmonary Hydatid Cyst and Aspergilloma: Case Report and Systematic Review

Pulmonary Aspergillus Overlap Syndromes

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