Dermatophytosis is a superficial fungal infection mostly restricted to keratinized tissues such as skin, hair and nails, but with potential to cause invasive or even systemic disease in immunocompromised patients. Trichophyton rubrum is the main etiologic agent, accounting for approximately 80% of the cases. Mononuclear phagocytes respond to pathogens through phagocytosis followed by production of several antimicrobial molecules, such as reactive oxygen and nitrogen species, and failure in doing so may contribute to development of chronic fungal infections. Toll like receptors (TLRs) located on the surface of phagocytic cells bind either directly to target particles or through opsonizing ligands, and trigger an actin-mediated ingestion. Even though the mechanisms involved in TLR-mediated cytokine responses are well established, the contribution of TLR in the recognition of T. rubrum by adherent monocytes remains unclear. Here, we report that phagocytosis of T. rubrum conidia by adherent monocytes is mediated by TLR2. Blockade of TLR2 by neutralizing antibodies impaired the fungicidal activity of monocytes as well their secretion of tumor necrosis factor (TNF)-α, but neither nitric oxide (NO) production nor interleukin (IL) – 10 secretion were disturbed. So far, our data suggest that TLR2 is required for efficient conidial phagocytosis and the absence of TLR2 signaling in human monocytes may impair the subsequent inflammatory response. These findings expand our understanding of phagocyte modulation by this important fungal pathogen and may represent a potential target for interventions aiming at enhancing antifungal immune responses.

Sporotrichosis is a subcutaneous infection caused by fungi from the genus Sporothrix, among which Sporothrix brasiliensis displays high virulence and transmissibility. So far, classical antifungal agents have been efficient against S. brasiliensis, but here we describe the first case of therapeutic failure and a high minimum inhibitory concentration (MIC) in relation to itraconazole.

CKD progression depends on the activation of an intricate set of hemodynamic and inflammatory mechanisms, promoting renal leukocyte infiltration, inflammation and fibrosis, leading to renal function loss. There are currently no specific drugs to detain fibrogenesis, which is a common end-point for different nephropathies. Clinical therapy for CKD is mostly based on the management of hypertension and proteinuria, partially achieved with renin-angiotensin-aldosterone system (RAAS) blockers, and the control of inflammation by immunosuppressive drugs. The aim of the present study was to verify if the administration of tamoxifen (TAM), an estrogen receptor modulator, clinically employed in the treatment of breast cancer and predicted to exert antifibrotic effects, would promote additional benefits when associated to a currently used therapeutic scheme for the conservative management of experimental CKD. Wistar rats underwent the NAME model of hypertensive nephrosclerosis, obtained by daily oral administration of a nitric oxide synthesis inhibitor, associated to dietary sodium overload. The therapeutic association of TAM to losartan (LOS), and mofetil mycophenolate (MMF) effectively reduced the severe hypertension, marked albuminuria and glomerular damage exhibited by NAME animals. Moreover, the association also succeeded in limiting renal inflammation in this model, and promoted further reduction of ECM interstitial accumulation and renal fibrosis, compared to the monotherapies. According to our results, the association of TAM to the currently used conservative treatment of CKD added significant antifibrotic effects both in vivo and in vitro , and may represent an alternative to slow the progression of chronic nephropathy.

Sporotrichosis, caused by a Sporothrix schenckii complex species, is historically viewed as an easily manageable mycosis. However, the current zoonotic epidemic in Brazil due to the more virulent Sporothrix brasiliensis poses some challenges. We describe three cases of lymphocutaneous sporotrichosis (LC) in non-immunocompromised patients, which proved refractory to standard treatment, and suggest that closer epidemic surveillance would be advisable to detect whether more difficult-to-treat cases are emerging. All cases required prolonged treatment, escalating doses, and therapeutic changes for resolution. Patients’ isolates were molecularly identified as S. brasiliensis. Antifungal susceptibility testing (AST) revealed high itraconazole MICs in two of the three isolates. Management required high-dose itraconazole (400 mg/day) in two cases and Amphotericin B in one. These cases challenge the perception of sporotrichosis as an always easily treatable disease. The difficulties observed may be linked to the increased S. brasiliensis virulence, the emergence of drug-resistant strains, and/or the rise in severe and atypical presentations. Lack of standardized protocols for refractory cases complicates effective management. These findings underscore the urgent need for enhanced epidemiological surveillance, efforts to isolate and perform AST on clinical strains, and standardization of treatment guidelines for patients failing initial therapy.