Eradicating, retaining, balancing, swarming, shuttling and dumping: a myriad of tasks for neutrophils during fungal infection

Urban, Constantin F.; Backman, Emelie

doi:10.1016/j.mib.2020.09.011

Cited by 19 publications

(18 citation statements)

References 73 publications

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“…Germinating conidia that escape macrophages are eliminated by recruited neutrophils and monocytes. Neutrophil extracellular traps (NETs) contribute to the innate host defence in vivo and neutrophils exert a considerable variety of antifungal effector functions, which include recognition, phagocytosis, intracellular clearance mediated by both oxidative and non-oxidative mechanisms, secretion of antimicrobial molecules and the release of neutrophil extracellular traps (NETs) ( Urban & Backman 2020 ). Failure to prevent conidial germination results in hyphal growth, tissue invasion, and marks the initiation of fungal disease.…”

Section: Virulence Immunology and Pathogenesis Of Aspergillusmentioning

confidence: 99%

Aspergillus fumigatusand aspergillosis: From basics to clinics

Arastehfar

Carvalho

Houbraken

et al. 2021

Studies in Mycology

146

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: Virulence Immunology and Pathogenesis Of Aspergillusmentioning

confidence: 99%

Aspergillus fumigatusand aspergillosis: From basics to clinics

Arastehfar

Carvalho

Houbraken

et al. 2021

Studies in Mycology

146

112

View full text Add to dashboard Cite

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“…22,25 In addition to affecting CD4 T cells, Sap can induce the vaginal epithelium to produce IL8, which plays a vital role in neutrophil migration and is essential for the host's defense against invasive fungal diseases. 19,26,27 In our clinical data analysis, the Sap activity of the RVVC strains was weaker than that of the VVC strains, possibly because the vaginal host environment induced by C. albicans with weak Sap was conducive to the growth and survival of C. albicans. This study selected two C. albicans fungi with the highest and weakest Sap activity to induce RVVC in mice assisted by estrogen.…”

Section: Discussionmentioning

confidence: 79%

“…IL4, a representative cytokine secreted by Th2 cells, can mediate the fluid immune response, produce proinflammatory factors, and increase susceptibility to infection 22,25 . In addition to affecting CD4 T cells, Sap can induce the vaginal epithelium to produce IL8, which plays a vital role in neutrophil migration and is essential for the host's defense against invasive fungal diseases 19,26,27 . In our clinical data analysis, the Sap activity of the RVVC strains was weaker than that of the VVC strains, possibly because the vaginal host environment induced by C. albicans with weak Sap was conducive to the growth and survival of C. albicans .…”

Section: Discussionmentioning

confidence: 90%

Analysis of pathogenic factors of Candida albicans and the effect of vaginal immunization on recurrent vulvovaginal candidiasis in mice

Shao

Hou

et al. 2021

J of Obstet and Gynaecol

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Background The role of fungal pathogenic factors and the immune response of the vaginal epithelium in vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are still unclear. Our study wants to clarify whether there are differences in pathogenic factors between VVC and RVVC strains, confirm the roles of pathogenic factors in the pathogenesis of RVVC, and analyze the influence of pathogenic factors on vaginal host immunity. Methods VVC‐ and RVVC‐causing Candida albicans strains were genotyped with 25S rDNA. Drug susceptibility assays using a modified alamarBlue broth microdilution method were carried out. Milk culture medium and egg yolk culture medium were used to measure the secreted aspartate protease (Sap) and phospholipase (Plb) activity of the samples. We used C. albicans with different Sap activity levels to induce RVVC in mice and measured interleukin 4 (IL4), interleukin 8 (IL8), and interleukin 17 (IL17) in vaginal lavage fluid at different stages of RVVC infection. Results There were no significant differences between VVC and RVVC fungi except that the Sap activity was lower for RVVC‐causing C. albicans than for VVC‐causing C. albicans. C. albicans with both strong Sap and weak Sap induced RVVC in mice. C. albicans with strong Sap had a reduced RVVC infection rate. In addition, C. albicans with strong Sap stimulated the vaginal epithelium to secrete more IL4, IL8, and IL17. Conclusion Compared with that of VVC‐causing C. albicans, the Sap activity of RVVC‐causing C. albicans was lower. C. albicans with strong Sap was less capable of causing repeated vaginal infections than that with weak Sap and stimulated the vaginal epithelium to produce more cytokines.

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“…Upon systemic candidiasis, the fungus encounters myeloid phagocytes, including neutrophils, inflammatory monocytes, tissue-resident macrophages, and dendritic cells (DCs), which mount strong innate defense ( 11 ). These effector cells act by phagocytosis and intracellular killing of C. albicans yeast cells by degranulation of antimicrobial molecules and neutrophil extracellular traps (NETs) formation to counteract extracellular fungal hyphae, production of both pro- and anti-inflammatory cytokines, and chemokines, AMPs, hydrolases, and nutritional immunity ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%