IFN-γ impairs Trichophyton rubrum proliferation in a murine model of dermatophytosis through the production of IL-1β and reactive oxygen species

• Published in: Medical mycology (Oxford) Vol. 52; no. 3; p. 293
• Main Authors: Baltazar, Ludmila de Matos, Santos, Patrícia Campi, Paula, Talles Prosperi de, Rachid, Milene Alvarenga, Cisalpino, Patrícia Silva, Souza, Danielle Glória, Santos, Daniel Assis
• Format: Journal Article
• Language: English
• Published: England 01.04.2014
• Subjects: Animals; Colony Count, Microbial; Disease Models, Animal; Interferon-gamma - metabolism; Interleukin-1beta - metabolism; Macrophages - immunology; Macrophages - microbiology; Male; Mice, Inbred C57BL; Mice, Knockout; Phagocytosis; Reactive Oxygen Species - metabolism; Skin - microbiology; Skin - pathology; Tinea - immunology; Tinea - microbiology; Tinea - pathology; Trichophyton - immunology; IFN-γ; dermatophytosis; IL-1β; T. rubrum
• ISSN: 1460-2709
• DOI: 10.1093/mmy/myt011

Trichophyton rubrum is the main etiological agent of dermatophytosis, an infection of the skin that affects millions of people worldwide. In this study, we developed a murine model of the dermatophytosis caused by T. rubrum in which C57BL/6 wild-type, interleukin (IL)-12(-/-), and interferon-gamma (IFN-γ(-/-)) mice were inoculated with 1 × 10(6) conidia/animal. The fungal burden, myeloperoxidase and N-acetylglucosaminidase activities, cytokine and chemokine profiles, and histopathology of the skin were evaluated on the seventh and fourteenth days post infection. Phagocytic indices, intracellular proliferation rates, and oxidative bursts generated by macrophages from WT and IFN-γ(-/-) mice were determined. On day 7 post infection, higher fungal burdens were observed comparison with burdens on day 14 post infection. The IL-12(-/-) and IFN-γ(-/-) mice showed higher fungal burdens on the skin and lower levels of IL-1β. Conversely, the WT mice showed lower fungal burdens with higher production of TNF-α, IL-1β, and chemokine ligand 1/keratinocyte chemoattractant (CXCL1/KC). The macrophages from WT mice proved to be more efficient at engulfing and killing T. rubrum conidia through the production of reactive oxygen species. The results show that our model is a useful tool for understanding the pathogenesis of dermatophytosis caused by T. rubrum and that IL-12 and IFN-γ are pivotal in controlling the infection through the recruitment and activation of neutrophils and macrophages.