Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis.
Chromoblastomycosis (CBM), a chronic subcutaneous infection caused by black fungi such as Fonsecaea monophora (F. monophora), is characterized by a low cure rate, high recurrence rate, and prolonged treatment duration. Neutrophils, one of the most important innate immune cells, play complex roles in...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-04-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0012986 |
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| author | Huan Huang Minying Li Yinghui Liu Yangxia Chen Zhenmou Xie Mingfen Luo Dongmei Li Hongfang Liu Liyan Xi |
| author_facet | Huan Huang Minying Li Yinghui Liu Yangxia Chen Zhenmou Xie Mingfen Luo Dongmei Li Hongfang Liu Liyan Xi |
| author_sort | Huan Huang |
| collection | DOAJ |
| description | Chromoblastomycosis (CBM), a chronic subcutaneous infection caused by black fungi such as Fonsecaea monophora (F. monophora), is characterized by a low cure rate, high recurrence rate, and prolonged treatment duration. Neutrophils, one of the most important innate immune cells, play complex roles in the prevention of fungal infections. This study investigated the function of neutrophils in host defense against F. monophora using a neutrophil-depleted mouse model and in vitro co-culture conditions. Fungal burden, histopathological changes, and cytokine profiles were compared between neutrophil-depleted mice and isotype control mice. Our findings demonstrated that neutrophil depletion in mice led to impaired fungal clearance, prolonged inflammation in F. monophora infected footpad tissues, highlighting the critical role of neutrophils in controlling F. monophora infection. Histopathological analysis revealed extensive inflammatory cell infiltration, especially macrophages, accompanied by elevated levels of pro-inflammatory cytokines such as IL-1β, CCL3, IL-6, and TNF-α. Besides, we observed that neutrophils play a key role in inhibiting the morphological transition of F. monophora from conidia to hyphae and sclerotic-like cells. Notably, the F. monophora morphology was also associated with the formation of neutrophil extracellular traps (NETs) in in vitro experiment. These findings underscore the importance of neutrophil-mediate immune responses in early fungal clearance and their ability to influence F.monophora morphological transition. The study provides novel insights into the immune mechanisms underlying CBM and highlights the potential therapeutic implications of targeting neutrophil-mediated responses in CBM infections. |
| format | Article |
| id | doaj-art-6f394a822dbd4bd0b71d31cff9dd717e |
| institution | OA Journals |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-6f394a822dbd4bd0b71d31cff9dd717e2025-08-20T02:20:03ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352025-04-01194e001298610.1371/journal.pntd.0012986Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis.Huan HuangMinying LiYinghui LiuYangxia ChenZhenmou XieMingfen LuoDongmei LiHongfang LiuLiyan XiChromoblastomycosis (CBM), a chronic subcutaneous infection caused by black fungi such as Fonsecaea monophora (F. monophora), is characterized by a low cure rate, high recurrence rate, and prolonged treatment duration. Neutrophils, one of the most important innate immune cells, play complex roles in the prevention of fungal infections. This study investigated the function of neutrophils in host defense against F. monophora using a neutrophil-depleted mouse model and in vitro co-culture conditions. Fungal burden, histopathological changes, and cytokine profiles were compared between neutrophil-depleted mice and isotype control mice. Our findings demonstrated that neutrophil depletion in mice led to impaired fungal clearance, prolonged inflammation in F. monophora infected footpad tissues, highlighting the critical role of neutrophils in controlling F. monophora infection. Histopathological analysis revealed extensive inflammatory cell infiltration, especially macrophages, accompanied by elevated levels of pro-inflammatory cytokines such as IL-1β, CCL3, IL-6, and TNF-α. Besides, we observed that neutrophils play a key role in inhibiting the morphological transition of F. monophora from conidia to hyphae and sclerotic-like cells. Notably, the F. monophora morphology was also associated with the formation of neutrophil extracellular traps (NETs) in in vitro experiment. These findings underscore the importance of neutrophil-mediate immune responses in early fungal clearance and their ability to influence F.monophora morphological transition. The study provides novel insights into the immune mechanisms underlying CBM and highlights the potential therapeutic implications of targeting neutrophil-mediated responses in CBM infections.https://doi.org/10.1371/journal.pntd.0012986 |
| spellingShingle | Huan Huang Minying Li Yinghui Liu Yangxia Chen Zhenmou Xie Mingfen Luo Dongmei Li Hongfang Liu Liyan Xi Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis. PLoS Neglected Tropical Diseases |
| title | Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis. |
| title_full | Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis. |
| title_fullStr | Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis. |
| title_full_unstemmed | Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis. |
| title_short | Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis. |
| title_sort | absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis |
| url | https://doi.org/10.1371/journal.pntd.0012986 |
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