Pro-inflammatory responses induced by <i>A. fumigatus</i> and <i>A. versicolor</i> in various human macrophage models

Øya, Elisabeth; Solhaug, Anita; Bølling, Anette Kocbach; Øvstebø, Reidun; Steensen, Tonje Berg; Afanou, Anani; Holme, Jørn A.

doi:10.1080/15287394.2019.1619114

Cited by 11 publications

(23 citation statements)

References 74 publications

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“…The pro‐inflammatory responses between mold species vary substantially, and growth conditions may change their potency, as exemplified in Table 1. In a study in human macrophage models, hyphal fragments of the pathogenic A fumigatus were found to induce cytokines at concentrations that were in the order 10 3 ‐10 4 lower than those from A fumigatus spores and from less pathogenic A versicolor hyphal fragments; however, a rather similar cytokine profiles were seen . Previous studies have reported similar differences between the two Aspergillus spp.…”

Section: Characterization and Pro‐inflammatory Potential Of Mold Partmentioning

confidence: 85%

“…The THP‐1 macrophage differentiation process provides several changes in phenotypes including loss of proliferation, increased adherence and changed expression of receptors . The THP‐1 macrophage model is very sensitive to both X‐ray‐killed spores and hyphal fragments and responds with a broad cytokine response seen at very low doses . However, PMA treatment also interferes with essential mechanisms of the cytokine production .…”

Section: Characterization and Pro‐inflammatory Potential Of Mold Partmentioning

confidence: 99%

“… a A rough simplification of the relative inflammatory responses (IL‐1β, IL‐6, and IL‐8 release) after exposure to A fumigatus (hyphal fragments or spores) seen in various human macrophage models as well as in BEAS‐2B lung epithelial cells based on studies, illustrating that the specific responses are highly depending on experimental system. …”

Section: Characterization and Pro‐inflammatory Potential Of Mold Partmentioning

confidence: 99%

“…Resting spores are often found to be more inert toward recognition by the immune system when compared to swelling spores and hyphae (102,(165)(166)(167)(168). This is partly due to pigments such as melanin and the rodlet layer composed of the hydrophobic RodA protein on the outer surface of spores.…”

Section: Mold Samplesmentioning

confidence: 99%

“…As the growth conditions may affect the molds pro-inflammatory potential (188), this type of testing should preferentially be done on environmental samples. Although individuals show characteristic allergy linked IgE immune responses for different mold ( 23), the cytokine profiles obtained after exposure to different mold species, as well as to either spores or hyphal fragments, seems to be rather similar (167,168). Thus, pattern of cytokine response in experimental systems or in human studies does not necessarily give a straight answer to the type of immune triggering causal agent.…”

Section: Accepted Articlementioning

confidence: 99%

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Characterization and pro‐inflammatory potential of indoor mold particles

et al. 2020

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A number of epidemiological studies find an association between indoor air dampness and respiratory health effects. This is often suggested to be linked to enhanced mold growth. However, the role of mold is obviously difficult to disentangle from other dampness‐related exposure including microbes as well as non‐biological particles and chemical pollutants. The association may partly be due to visible mycelial growth and a characteristic musty smell of mold. Thus, the potential role of mold exposure should be further explored by evaluating information from experimental studies elucidating possible mechanistic links. Such studies show that exposure to spores and hyphal fragments may act as allergens and pro‐inflammatory mediators and that they may damage airways by the production of toxins, enzymes, and volatile organic compounds. In the present review, we hypothesize that continuous exposure to mold particles may result in chronic low‐grade pro‐inflammatory responses contributing to respiratory diseases. We summarize some of the main methods for detection and characterization of fungal aerosols and highlight in vitro research elucidating how molds may induce toxicity and pro‐inflammatory reactions in human cell models relevant for airway exposure. Data suggest that the fraction of fungal hyphal fragments in indoor air is much higher than that of airborne spores, and the hyphal fragments often have a higher pro‐inflammatory potential. Thus, hyphal fragments of prevalent mold species with strong pro‐inflammatory potential may be particularly relevant candidates for respiratory diseases associated with damp/mold‐contaminated indoor air. Future studies linking of indoor air dampness with health effects should assess the toxicity and pro‐inflammatory potential of indoor air particulate matter and combined this information with a better characterization of biological components including hyphal fragments from both pathogenic and non‐pathogenic mold species. Such studies may increase our understanding of the potential role of mold exposure.

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Section: Characterization and Pro‐inflammatory Potential Of Mold Partmentioning

confidence: 85%

Section: Characterization and Pro‐inflammatory Potential Of Mold Partmentioning

confidence: 99%

Section: Characterization and Pro‐inflammatory Potential Of Mold Partmentioning

confidence: 99%

Section: Mold Samplesmentioning

confidence: 99%

Section: Accepted Articlementioning

confidence: 99%

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Characterization and pro‐inflammatory potential of indoor mold particles

et al. 2020

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Innate and Adaptive Immune Responses Induced by Aspergillus fumigatus Conidia and Hyphae

et al. 2022

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Previous research indicated that hyphae of Aspergillus fumigatus ( A. fumigatus ) rather than conidia could successfully build a pulmonary aspergillosis model in immunocompetent mice. In this study, we compared the immune responses induced by hyphae and conidia to explore the possible mechanism of this striking phenomenon. Herein, a novel method was designed and adopted to quantify hyphal fragments. Murine macrophages RAW264.7 and human peripheral blood mononuclear cells were stimulated by A. fumigatus hyphae and conidia in vitro, respectively, and then immunological reactions were measured. Male C57BL/6 mice were challenged with conidia and hyphae through intratracheal inoculation. Dynamic conditions of mice were recorded, and RNA-seq measured corresponding immune responses. The results of the study confirmed that hyphae could induce more intensive inflammation than conidia in vitro and in vivo. However, macrophages revealed a higher production of ROS and M1 polarisation in response to conidia stimuli. Additionally, conidia could promote Th1 cell differentiation, while hyphae could increase the CD4/CD8 ratio. RNA-seq validated the fact that those multiple immunologically relevant pathways were more strongly activated by hyphae than conidia, which also promoted Th2 cell differentiation and suppressed Th1 signalling. Both hyphae and conidia could activate Th17 signalling. In general, conidia and hyphae induced distinctly different host immune responses, and the immune responses induced by conidia played a better protective effect. Therefore, the unique function of hyphae in the spread and infection of Aspergillus should be emphasised, and more research is required to clarify the underlying mechanisms for better understanding and management of aspergillosis. Supplementary Information The online version contains supplementary material available at 10.1007/s00284-022-03102-1.

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