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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 <jats:italic>F. monophora<\/jats:italic> using a neutrophil-depleted mouse model and <jats:italic>in vitro<\/jats:italic> 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 <jats:italic>F. monophora<\/jats:italic> infected footpad tissues, highlighting the critical role of neutrophils in controlling <jats:italic>F. monophora<\/jats:italic> infection. Histopathological analysis revealed extensive inflammatory cell infiltration, especially macrophages, accompanied by elevated levels of pro-inflammatory cytokines such as IL-1\u03b2, CCL3, IL-6, and TNF-\u03b1. Besides, we observed that neutrophils play a key role in inhibiting the morphological transition of <jats:italic>F. monophora<\/jats:italic> from conidia to hyphae and sclerotic-like cells. Notably, the <jats:italic>F. monophora<\/jats:italic> morphology was also associated with the formation of neutrophil extracellular traps (NETs) in <jats:italic>in vitro<\/jats:italic> experiment. These findings underscore the importance of neutrophil-mediate immune responses in early fungal clearance and their ability to influence <jats:italic>F.monophora<\/jats:italic> 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.<\/jats:p>","DOI":"10.1371\/journal.pntd.0012986","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:26:15Z","timestamp":1745429175000},"page":"e0012986","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4833-2883","authenticated-orcid":true,"given":"Huan","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minying","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinghui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangxia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenmou","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingfen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4352-2533","authenticated-orcid":true,"given":"Hongfang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyan","family":"Xi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"pntd.0012986.ref001","volume-title":"Report of the Tenth Meeting of the WHO Strategic and Technical Advisory Group for Neglected Tropical Diseases. 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