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. 2024 Jun 14;10(6):422.
doi: 10.3390/jof10060422.

Neutrophil Oxidative Burst Profile Is Related to a Satisfactory Response to Itraconazole and Clinical Cure in Feline Sporotrichosis

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Neutrophil Oxidative Burst Profile Is Related to a Satisfactory Response to Itraconazole and Clinical Cure in Feline Sporotrichosis

Luisa Helena Monteiro de Miranda et al. J Fungi (Basel). .

Abstract

Despite the central role of cats in the transmission and amplification of Sporothrix, studies regarding immune response in feline sporotrichosis are scarce. In cats with sporotrichosis, neutrophil-rich lesions are usually associated to good general condition and lower fungal burden. However, the role of neutrophils in anti-Sporothrix immunity has been little explored in cats. Thus, the aim of this study was to evaluate the neutrophil oxidative burst in the blood of cats with sporotrichosis. Cats with sporotrichosis included in the study were treated with itraconazole (ITZ) alone or combined with potassium iodide (KI). The neutrophil oxidative burst was evaluated through a flow-cytometry-based assay using dihydrorhodamine 123 (background) and stimulation with Zymosan and heat-killed Sporothrix yeasts. The cure rate was 50.0% in cats under treatment with ITZ monotherapy and 90.9% in cats treated with ITZ + KI (p = 0.014), endorsing the combination therapy as an excellent alternative for the treatment of feline sporotrichosis. Higher percentages of Sporothrix-stimulated neutrophils were associated with good general condition (p = 0.003). Higher percentages of Sporothrix- (p = 0.05) and Zymosan-activated (p = 0.014) neutrophils before and early in the treatment were related to clinical cure in ITZ-treated cats. The correlation between oxidative burst and successful use of KI could not be properly assessed given the low number of failures (n = 2) in this treatment group. Nasal mucosa involvement, typically linked to treatment failure, was related to lower percentages of activated neutrophils in the background at the treatment outcome (p = 0.02). Our results suggest a beneficial role of neutrophils in feline sporotrichosis and a positive correlation between neutrophil activation and the cure process in ITZ-treated cats.

Keywords: Sporothrix; cat; flow cytometry; neutrophils; oxidative burst; sporotrichosis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Feline sporotrichosis. Skin lesions in cats presented at Lapclin-Dermzoo/INI/Fiocruz, Rio de Janeiro, Brazil. Disseminated skin lesions (A); Multiple skin ulcers on the face (B); Skin ulcers on the forelimb (C); Swelling over the bridge of the nose (D).
Figure 2
Figure 2
Feline sporotrichosis. Response to treatment. Clinical cure. Cat presenting multiple skin ulcers on the face before the beginning of the treatment (A) and complete healing after eighteen weeks of treatment with the combination of itraconazole and KI (B); Cat presenting swelling over the bridge of the nose and a skin ulcer at the palmar side of the left forelimb before the beginning of the treatment (C) and complete healing and the remission of clinical signs after twenty-nine weeks of treatment with itraconazole (D); Cat presenting ulcerated lesion on the right forelimb pad before the beginning of the treatment (E) and complete healing after sixteen weeks of treatment with itraconazole (F).
Figure 3
Figure 3
Feline sporotrichosis. Response to treatment. Treatment failure. Cat presenting swelling and ulceration on the bridge of the nose and periocular skin lesions before the beginning of the treatment (A); and the persistence of the skin lesion on the bridge of the nose after eight weeks of treatment with itraconazole (B); Cat presenting skin ulcer lateral to the nose and nasal planum before the beginning of the treatment (C); and persistence of the lesion with the swelling of the nose and the appearance of multiple nodules on the left ear after sixteen weeks of treatment with the combination of itraconazole and KI (D).
Figure 4
Figure 4
The neutrophil oxidative burst test performed on the peripheral blood of cats with sporotrichosis demonstrates a significant variation in some neutrophil oxidative burst parameters, depending on clinical and therapeutic features. Good general condition is associated (pMW = 0.003) with a higher percentage of Sporothrix-stimulated neutrophils at T1 (A); Clinical cure with combination therapy is associated (pMW = 0.035) with a higher stimulation index in Sporothrix-stimulated neutrophils at T2 in comparison to monotherapy (B); Clinical cure with monotherapy is associated (pMW = 0.05) with a higher percentage of Sporothrix-stimulated neutrophils at T1 in comparison to treatment failure (C); The percentage of Zymosan-stimulated neutrophils is significantly higher (pF = 0.014) in T2 in comparison to T1 in clinical cure in comparison to treatment failure (D); The percentage of positive neutrophils in the background control at T2 is significantly higher (pMW = 0.03) in clinical cure with monotherapy in comparison to treatment failure (E); Nasal mucosa involvement is associated (pMW = 0.02) with a lower percentage of positive neutrophils in the background control at T3 in cats submitted to the monotherapy (F).

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