Background Trichosporon asahii (T. asahii) is a lethal pathogen that infects immunocompromised individuals. This study aimed to investigate the PLB1-mediated invasion mechanism of T. asahii in lung epithelial cells. Methods Recombinant PLB1 protein was purified and used to stimulate alveolar type II (AT-II) cells. Following, transcriptome sequencing was performed to identify downstream targets. Cells were infected with PLB1-overexpressing (PLB1OX) T. asahii and transfected with overexpression vectors for Cav1 (Cav1OE) and/or Arg2 (Arg2OE). Subsequently, the activation of JAK/STAT3 signaling, expression of arginine metabolic markers, inflammation levels, cell viability, membrane integrity, and co-localization of Cav1 with fungi were assessed. L-arginine and L-proline levels were quantified by high performance liquid chromatography. In vivo, immunosuppressed mice were injected with PLB1OX T. asahii and a Cav1OE vector. Lung pathology and internalized fungi were evaluated using hematoxylin–eosin and periodic acid-schiff staining, respectively. Arginine metabolism, inflammation, and fibrosis in lung tissues were assessed using the same methods. Results Recombinant PLB1 significantly inhibited AT-II cell viability. Infection with PLB1OX T. asahii promoted fungi internalization, disrupted membrane integrity, downregulated Cav1 expression, and activated both JAK/STAT3 signaling and arginine synthesis pathways in lung epithelial cells. The addition of a JAK2 agonist blocked the suppressive effects of Cav1 overexpression on JAK/STAT3 signaling and arginine metabolism in PLB1OX T. asahii-infected AT-II cells. Downstream, Arg2 was predicted as a potential target for Cav1 to exert its biological functions. Further in vitro experiments confirmed that Arg2 overexpression counteracted the increased antifungal capacity conferred by Cav1 overexpression. In mouse lung tissues, PLB1OX T. asahii infection downregulated Cav1, while enhancing JAK-STAT3 activation, arginine synthesis, inflammation, and fibrosis. These pathological and molecular changes were alleviated by Cav1 overexpression. Conclusions PLB1OX T. asahii impaired antifungal defenses in lung epithelial cells through the Cav1/JAK/STAT3-mediated arginine metabolism, while triggering inflammation and fibrosis.

PLB1 enhances adhesion and invasion of Trichosporon asahii to lung epithelial cells: insights into the mechanisms of Cav1/JAK/STAT3-induced arginine metabolism

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2026年1月23日

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He Zhu,
Junhong Ao,
Xiaoxian Cheng,
Xin Yang,
Haitao Li,
Rongya Yang

摘要

Background

Trichosporon asahii (T. asahii) is a lethal pathogen that infects immunocompromised individuals. This study aimed to investigate the PLB1-mediated invasion mechanism of T. asahii in lung epithelial cells.

Methods

Recombinant PLB1 protein was purified and used to stimulate alveolar type II (AT-II) cells. Following, transcriptome sequencing was performed to identify downstream targets. Cells were infected with PLB1-overexpressing (PLB1^OX) T. asahii and transfected with overexpression vectors for Cav1 (Cav1^OE) and/or Arg2 (Arg2^OE). Subsequently, the activation of JAK/STAT3 signaling, expression of arginine metabolic markers, inflammation levels, cell viability, membrane integrity, and co-localization of Cav1 with fungi were assessed. L-arginine and L-proline levels were quantified by high performance liquid chromatography. In vivo, immunosuppressed mice were injected with PLB1^OX T. asahii and a Cav1^OE vector. Lung pathology and internalized fungi were evaluated using hematoxylin–eosin and periodic acid-schiff staining, respectively. Arginine metabolism, inflammation, and fibrosis in lung tissues were assessed using the same methods.

Results

Recombinant PLB1 significantly inhibited AT-II cell viability. Infection with PLB1^OX T. asahii promoted fungi internalization, disrupted membrane integrity, downregulated Cav1 expression, and activated both JAK/STAT3 signaling and arginine synthesis pathways in lung epithelial cells. The addition of a JAK2 agonist blocked the suppressive effects of Cav1 overexpression on JAK/STAT3 signaling and arginine metabolism in PLB1^OX T. asahii-infected AT-II cells. Downstream, Arg2 was predicted as a potential target for Cav1 to exert its biological functions. Further in vitro experiments confirmed that Arg2 overexpression counteracted the increased antifungal capacity conferred by Cav1 overexpression. In mouse lung tissues, PLB1^OX T. asahii infection downregulated Cav1, while enhancing JAK-STAT3 activation, arginine synthesis, inflammation, and fibrosis. These pathological and molecular changes were alleviated by Cav1 overexpression.

Conclusions

PLB1^OX T. asahii impaired antifungal defenses in lung epithelial cells through the Cav1/JAK/STAT3-mediated arginine metabolism, while triggering inflammation and fibrosis.