Study of the temperature-related factors that activate the NLRP3 inflammasome in Trichophyton schoenleinii and their activation mechanisms.

INTRODUCTION

To investigate whether the temperature regulatory factor of Trichophyton schoenleinii (T. schoenleinii) is involved in the activation of the NLRP3 inflammasome and the regulation of related signaling pathways and to elucidate the unique pathogenesis of tinea capitis in Xinjiang.

METHODS

T. schoenleinii (strain 30076) isolated from patients with favus was subjected to heat stress at 42 °C and 37 °C, with normal temperature (27 °C) used as a control. Transcriptome sequencing and bioinformatics analysis were performed. A key temperature regulatory factor was screened, and a silencing strain was constructed. THP-1 cells were treated with a ROS inhibitor, a cathepsin inhibitor, high potassium, or RNA interference targeting NLRP3 and ASC and then infected with the wild-type or strains. The expression of IL-1β, IL-18, NLRP3, ASC, and Caspase-1 was detected.

RESULTS

Differentially expressed genes under heat stress were enriched in metabolic pathways and heat shock protein-related genes. TRINITY_DN3793_c0_g1 was identified as a temperature regulatory factor. T. schoenleinii induced the expression of IL-1β, IL-18, and NLRP3-related molecules in THP-1 cells, a process regulated by ROS, cathepsin, and potassium efflux. The temperature regulatory factor participated in but was not the sole requirement for NLRP3 inflammasome activation. The expression of related factors and ASC oligomerization were significantly lower in the silenced strain group than in the wild-type group.

DISCUSSION: Increased thermal stress causes severe mycelial damage in T. schoenleinii. Transcriptomics identifies TRINITY_DN3793_c0_g1 as a key temperature regulator. Infection activates the NLRP3 inflammasome via ROS, cathepsin B, and potassium efflux, promoting IL-1β/IL-18 secretion and ASC oligomerization. This regulator participates but is not essential for inflammasome activation. Findings reveal molecular links between temperature adaptation and pathogenicity, offering insights into tinea capitis pathogenesis and therapeutic targets.