Sporotrichosis is a deep fungal infection caused by Sporothrix species. Currently, itraconazole is the main treatment, but fungal resistance, adverse effects, and drug interactions remain major concerns, especially in patients with immune dysfunction. Therefore, an alternative treatment is greatly in demand. This animal study aimed to investigate the inhibitory effect of neodymium-doped yttrium aluminum garnet (Nd:YAG) 1,064-nm laser treatment on Sporothrix globosa and to explore whether it happens through regulation of the Nod-like receptor thermoprotein domain-related protein 3 (NLRP3)/caspase-1 pyroptosis and apoptosis pathway. After laser irradiation, a series of studies, including assays of viability (using the cell counting kit-8 [CCK-8]), morphological structure changes, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential, oxidative stress, cell cycle progression, and metacaspase activation, were conducted to estimate the effect of Nd:YAG 1,064-nm laser treatment on Sporothrix globosa cell apoptosis in vitro. For in vivo studies, mice were infected with S. globosa and then treated with laser or itraconazole, and their footpad skin lesions and the changes in the histology of tissue samples were compared. In addition, changes in the levels of NLRP3, caspase-1, and caspase-3 were assessed by immunohistochemistry, while the levels of interleukin 17 (IL-17), interferon gamma (IFN-γ), and transforming growth factor β1 (TGF-β1) in peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). The in vitro growth of S. globosa was inhibited and apoptosis was observed after laser treatment. According to the in vivo studies, the efficacy of the laser treatment was similar to that of itraconazole. Moreover, the NLRP3/caspase-1 pyroptosis pathway was activated, with a Th1/Th17 cell response, and the expression of caspase-3 was also upregulated. Nd:YAG 1,064-nm laser treatment can effectively inhibit the growth of S. globosa by activating fungal apoptosis and pyroptosis through the NLRP3/caspase-1 pathway. Therefore, Nd:YAG 1,064-nm laser irradiation is an alternative for sporotrichosis therapy. IMPORTANCE Nd:YAG 1,064-nm laser irradiation is a useful alternative for the treatment of sporotrichosis, especially in patients with liver dysfunction, pregnant women, and children, for whom the administration of antifungal drugs is not suitable. It may improve the overall treatment effect by shortening the duration of antifungal treatment and reducing tissue inflammation.

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