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Microfluidic Tools for Probing Fungal-Microbial Interactions at the Cellular Level
Published on: June 23, 2022
Interactions of human phagocytes with moulds Fusarium spp. and Verticillium nigrescens possessing different
Richard M Winn1, Cristina Gil-Lamaignere, Avgi Maloukou
1Third Department of Paediatrics, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
Abstract:
Fusarium spp. are emerging as important causes of invasive fungal infections. They tend to have decreased susceptibility to antifungal agents, making host defences very important. The ability of human phagocytes to cause damage to hyphae of Fusarium solani, F. oxysporum and Verticillium nigrescens, a mould with very low pathogenicity, was assessed using the 2,3-bis[2-methoxy-4-nitro-5-sulphophenyl]2H-tetrazolium-5-carboxanilide (XTT) metabolic assay. The oxidative burst, evidenced as superoxide anion (O2-) production, of phagocytes in response to hyphae was also investigated, as well as phagocytosis of conidia by monocyte (MNC)-derived macrophages (MDM). Hyphal damage by polymorphonuclear leukocytes (PMNL) and MNC showed a linear trend increasing with effector cell:target cell (E:T) ratio. Although no significant differences were observed for PMNL, MNC-induced damage to F. solani hyphae was lower than that seen with F. oxysporum hyphae at an E:T ratio of 20:1 and with V. nigrescens hyphae at ratios of 1:1, 5:1 and 20:1 (P < 0.05). In contrast, levels of O2- production by phagocytes in response to F. oxysporum were lower than those induced in response to the other fungi (P < 0.01). The average number of V. nigrescens conidia ingested by MDM was higher than that of conidia of the other fungi (P < 0.01). Phagocytes respond to the test fungi differentially, with F. solani being the least susceptible to damage by MNC. This may correlate with the observation that, compared to the other fungi studied, it causes a relatively high incidence of infections in neutropenic patients.
Insights
Human phagocytes show varied responses to Fusarium fungi, with Fusarium solani being least susceptible to damage. This differential response highlights the importance of host defenses against invasive fungal infections, especially in neutropenic patients.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Fusarium species are increasingly recognized as significant pathogens causing invasive fungal infections.
- These fungi often exhibit reduced susceptibility to antifungal medications, underscoring the critical role of host immune defenses.
- Understanding the interaction between human phagocytes and Fusarium is crucial for managing these infections.
Purpose of the Study:
- To evaluate the capacity of human phagocytes to damage Fusarium hyphae and conidia.
- To investigate the oxidative burst response of phagocytes upon exposure to different Fusarium species.
- To compare the phagocytic activity of monocyte-derived macrophages (MDM) against Fusarium conidia.
Main Methods:
- Utilized the XTT metabolic assay to quantify hyphal damage induced by polymorphonuclear leukocytes (PMNL) and monocyte (MNC)-derived macrophages (MDM).
- Measured superoxide anion (O2-) production as an indicator of the oxidative burst in phagocytes.
- Assessed the phagocytosis of fungal conidia by MDM.
Main Results:
- Phagocyte-induced hyphal damage increased linearly with the effector cell:target cell (E:T) ratio.
- MNCs showed significantly lower damage to Fusarium solani hyphae compared to Fusarium oxysporum and Verticillium nigrescens at specific E:T ratios.
- Phagocyte O2- production was lowest in response to F. oxysporum, while MDM ingested significantly more V. nigrescens conidia than other fungal species.
Conclusions:
- Human phagocytes exhibit differential responses to Fusarium species, with F. solani demonstrating the highest resistance to MNC-mediated damage.
- These findings suggest that the reduced susceptibility of F. solani to phagocytic damage may contribute to its higher incidence of infections in neutropenic patients.
- The study highlights the complex interplay between fungal virulence factors and host immune mechanisms in invasive fungal infections.
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