Crotoxin modulates Encephalitozoon cuniculi-infected macrophages toward the M1 microbicidal profile

Area of Science:

• Immunology
• Parasitology
• Pharmacology

Background:

• Microsporidia are opportunistic intracellular fungi resistant to conventional drugs.
• Microsporidia can evade macrophage microbicidal activity by shifting M1 macrophages to an M2 profile.
• Crotoxin (CTX), from Crotalus durissus terrificus, exhibits antibacterial, antitumor, and anti-inflammatory properties.

Purpose of the Study:

• To evaluate the effects of CTX on Encephalitozoon cuniculi spore viability.
• To assess CTX's impact on the microbicidal activity of macrophages infected with E. cuniculi.

Main Methods:

• E. cuniculi spores were treated with CTX (2.4 and 4.8 μg/mL) for viability analysis.
• Murine peritoneal macrophages were infected with E. cuniculi and treated with CTX.
• Macrophage profiles, cytokine production (TNF-α, IL-6), and spore proliferation were evaluated.

Main Results:

• CTX showed no direct fungicidal or fungistatic effect on E. cuniculi spores.
• CTX treatment (2.4 μg/mL) increased the M1 macrophage profile in infected cells.
• CTX enhanced necrosis in infected macrophages and increased TNF-α and IL-6 production, reducing spore proliferation.

Conclusions:

• CTX modulates the macrophage M1 profile against E. cuniculi infection.
• CTX enhances the production of proinflammatory cytokines, leading to increased microbicidal activity.
• CTX shows potential as an immunomodulatory agent against microsporidiosis.