Usefulness of animal models of aspergillosis in studying immunity against Aspergillus infections

Mirkov, Ivana; Aleksandrov, Aleksandra Popov; Lazović, Bojana; Glamočlija, Jasmina; Kataranovski, Milena

doi:10.1016/j.mycmed.2019.01.006

Cited by 8 publications

(9 citation statements)

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“…Technical aspects and the need for standardisation have been extensively reviewed recently by several authors ( Paulussen et al. 2014 , Desoubeaux & Cray 2017 , 2018 , Banfalvi 2018 , Mirkov et al. 2019 ).…”

Section: Application Of Murine and Insect Models To Identify Virulence Determinants And Antifungal Resistancementioning

confidence: 99%

Aspergillus fumigatusand aspergillosis: From basics to clinics

Arastehfar

Carvalho

Houbraken

et al. 2021

Studies in Mycology

158

112

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The airborne fungus Aspergillus fumigatus poses a serious health threat to humans by causing numerous invasive infections and a notable mortality in humans, especially in immunocompromised patients. Mould-active azoles are the frontline therapeutics employed to treat aspergillosis. The global emergence of azole-resistant A . fumigatus isolates in clinic and environment, however, notoriously limits the therapeutic options of mould-active antifungals and potentially can be attributed to a mortality rate reaching up to 100 %. Although specific mutations in CYP 51A are the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-type CYP 51A genotype challenging the efficacy of the current diagnostic tools. Therefore, applications of whole-genome sequencing are increasingly gaining popularity to overcome such challenges. Prominent echinocandin tolerance, as well as liver and kidney toxicity posed by amphotericin B, necessitate a continuous quest for novel antifungal drugs to combat emerging azole-resistant A . fumigatus isolates. Animal models and the tools used for genetic engineering require further refinement to facilitate a better understanding about the resistance mechanisms, virulence, and immune reactions orchestrated against A . fumigatus . This review paper comprehensively discusses the current clinical challenges caused by A . fumigatus and provides insights on how to address them.

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Section: Application Of Murine and Insect Models To Identify Virulence Determinants And Antifungal Resistancementioning

confidence: 99%

Aspergillus fumigatusand aspergillosis: From basics to clinics

Arastehfar

Carvalho

Houbraken

et al. 2021

Studies in Mycology

158

112

View full text Add to dashboard Cite

show abstract

“…The explanation of that phenomenon remains elusive. Animal models have shown that defence against Aspergillus is a multistep process 16 . Phagocyte recruitment represents only part of this immunity.…”

Section: Discussionmentioning

confidence: 99%

Recurrent bacterial infections, but not fungal infections, characterise patients with ELANE‐related neutropenia: a French Severe Chronic Neutropenia Registry study

et al. 2021

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Among 143 patients with elastase, neutrophil-expressed (ELANE)-related neutropenia enrolled in the French Severe Chronic Neutropenia Registry, 94 were classified as having severe chronic neutropenia (SCN) and 49 with cyclic neutropenia (CyN). Their infectious episodes were classified as severe, mild or oral, and analysed according to their natural occurrence without granulocyte-colony stimulating factor (G-CSF), on G-CSF, after myelodysplasia/acute leukaemia or after haematopoietic stem-cell transplantation. During the disease's natural history period (without G-CSF; 1913 person-years), 302, 957 and 754 severe, mild and oral infectious events, respectively, occurred. Among severe infections, cellulitis (48%) and pneumonia (38%) were the most common. Only 38% of episodes were microbiologically documented. The most frequent pathogens were Staphylococcus aureus (37Á4%), Escherichia coli (20%) and Pseudomonas aeruginosa (16%), while fungal infections accounted for 1%. Profound neutropenia (<200/ mm 3 ), high lymphocyte count (>3000/mm 3 ) and neutropenia subtype were associated with high risk of infection. Only the p.Gly214Arg variant (5% of the patients) was associated with infections but not the overall genotype. The first year of life was associated with the highest infection risk throughout life. G-CSF therapy achieved lower ratios of serious or oral infectious event numbers per period but was less protective for patients requiring >10 µg/kg/day. Infections had permanent consequences in 33% of patients, most frequently edentulism.

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“…Cytokines produced by Th17 inducing the expression of chemokines, which either destruct the pathogen or cause inflammation. 17,18…”

Section: Induction and Differentiation Of Th17mentioning

confidence: 99%

“…IL‐12, IFN‐γ and IL‐4 inducing differentiation of naive CD4+ T cells into Th1 and Th2 lineages, whereas IL‐6 along with TGF‐β inducing differentiation of Th17 cells via expression of transcription factors (T‐bet, ROR‐γt or GATA3). Cytokines produced by Th17 inducing the expression of chemokines, which either destruct the pathogen or cause inflammation 17,18 …”

Section: Induction and Differentiation Of Th17mentioning

confidence: 99%