Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in Mouse

BackgroundThe relationship between infection and tumors has attracted increasing attention. Trichoderma spp. are often isolated from tumors. However, their potential role remains unclear. We recently reported the isolation of Trichoderma longibrachiatum from a patient with pulmonary spindle cell car...

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Main Authors: Gongjie Zhang, Dongming Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2022.865722/full
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author Gongjie Zhang
Dongming Li
author_facet Gongjie Zhang
Dongming Li
author_sort Gongjie Zhang
collection DOAJ
description BackgroundThe relationship between infection and tumors has attracted increasing attention. Trichoderma spp. are often isolated from tumors. However, their potential role remains unclear. We recently reported the isolation of Trichoderma longibrachiatum from a patient with pulmonary spindle cell carcinoma that was confirmed as primary infection by application of laser capture microdissection and polymerase chain reaction. To explore whether the strain is pathogenic and whether it can cause atypical cell proliferation and infiltration of NK cells and T cells, we designed a mouse infection experiment.MethodsTwelve ICR mice were randomly separated into three groups. Cyclophosphamide was used to inhibit the immunity of mice. A mouse model of Trichoderma infection was successfully established by intracutaneous injection on the back skin with a suspension of strain PKUT180420015. The pathological manifestations of Trichoderma infection and the interaction between immune cells and fungi were observed by histopathology, immunohistochemistry and intensive fungal staining. Reisolation of the fungus was observed by infected tissue culture. The inoculated sites exhibited swelling 3 days after inoculation, and ulcers developed at approximately 14 days. Skin specimens were obtained and then cultured at 3, 7, and 14 days after inoculation. We selected mice 14 days after inoculation in Group 3, whose ulcers were the most typical, for histological analysis.ResultsInflammation, angioinvasion and necrosis were observed. Immunohistochemistry showed positive markers of Ki67, CD3, CD56, GZMB, and PRF. Periodic acid-Schiff staining, periodic acid-silver methenamine staining, and Calcofluor staining showed fungal spores in the vascular lumen, vascular walls and around the blood vessels.ConclusionsOur studies showed that a T. longibrachiatum strain (PKUT180420015) isolated from a biopsy specimen in a patient with pulmonary spindle cell carcinoma could induce atypical hyperplasia, with the expression of Ki67, CD3, CD56, GZMB, and PRF in mice. These data indicate that the fungus may be involved in inducing atypical hyperplasia or tumorigenesis.
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spelling doaj.art-3f64823ffcd14d7b96ef5b0d21429a532022-12-22T02:07:26ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-04-01910.3389/fmed.2022.865722865722Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in MouseGongjie ZhangDongming LiBackgroundThe relationship between infection and tumors has attracted increasing attention. Trichoderma spp. are often isolated from tumors. However, their potential role remains unclear. We recently reported the isolation of Trichoderma longibrachiatum from a patient with pulmonary spindle cell carcinoma that was confirmed as primary infection by application of laser capture microdissection and polymerase chain reaction. To explore whether the strain is pathogenic and whether it can cause atypical cell proliferation and infiltration of NK cells and T cells, we designed a mouse infection experiment.MethodsTwelve ICR mice were randomly separated into three groups. Cyclophosphamide was used to inhibit the immunity of mice. A mouse model of Trichoderma infection was successfully established by intracutaneous injection on the back skin with a suspension of strain PKUT180420015. The pathological manifestations of Trichoderma infection and the interaction between immune cells and fungi were observed by histopathology, immunohistochemistry and intensive fungal staining. Reisolation of the fungus was observed by infected tissue culture. The inoculated sites exhibited swelling 3 days after inoculation, and ulcers developed at approximately 14 days. Skin specimens were obtained and then cultured at 3, 7, and 14 days after inoculation. We selected mice 14 days after inoculation in Group 3, whose ulcers were the most typical, for histological analysis.ResultsInflammation, angioinvasion and necrosis were observed. Immunohistochemistry showed positive markers of Ki67, CD3, CD56, GZMB, and PRF. Periodic acid-Schiff staining, periodic acid-silver methenamine staining, and Calcofluor staining showed fungal spores in the vascular lumen, vascular walls and around the blood vessels.ConclusionsOur studies showed that a T. longibrachiatum strain (PKUT180420015) isolated from a biopsy specimen in a patient with pulmonary spindle cell carcinoma could induce atypical hyperplasia, with the expression of Ki67, CD3, CD56, GZMB, and PRF in mice. These data indicate that the fungus may be involved in inducing atypical hyperplasia or tumorigenesis.https://www.frontiersin.org/articles/10.3389/fmed.2022.865722/fullTrichoderma longibrachiatumtrichodermasisproliferationmouse experimentcarcinoma
spellingShingle Gongjie Zhang
Dongming Li
Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in Mouse
Frontiers in Medicine
Trichoderma longibrachiatum
trichodermasis
proliferation
mouse experiment
carcinoma
title Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in Mouse
title_full Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in Mouse
title_fullStr Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in Mouse
title_full_unstemmed Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in Mouse
title_short Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in Mouse
title_sort trichoderma longibrachiatum associated skin inflammation and atypical hyperplasia in mouse
topic Trichoderma longibrachiatum
trichodermasis
proliferation
mouse experiment
carcinoma
url https://www.frontiersin.org/articles/10.3389/fmed.2022.865722/full
work_keys_str_mv AT gongjiezhang trichodermalongibrachiatumassociatedskininflammationandatypicalhyperplasiainmouse
AT dongmingli trichodermalongibrachiatumassociatedskininflammationandatypicalhyperplasiainmouse