Invasive candidiasis encompassing Candida bloodstream infections and deep-seated candidiasis can become a persistent health problem. These infections are caused by Candida species and have high morbidity and mortality rates. Species distribution, access to diagnosis, treatment and mortality are different around the world. The mortality rate is high in South America (30–70%), and Candida albicans is the most prevalent species in this region. However, a global epidemiological shift to non-albicans species has been observed. In this group, C. parapsilosis is the species most frequently detected, followed by C. tropicalis, and at a slower rate, C. glabrata, which has also increased, in addition to the emerging C. auris, resistance to several drugs. This article summarizes relevant aspects of candidemia pathogenesis, such as the mechanisms of fungal invasion, immune response, and the impact of genetic defects that increase host susceptibility to developing the infection. We also discuss relevant aspects of treatment and future challenges in South America.

Vulvovaginal candidiasis (VVC) is a mucosal infection predominantly caused by Candida albicans, affecting over three-quarters of immunocompetent women worldwide. While the female genital tract mucosa is the primary defense against the fungus, the specific immune mechanisms involved in this host-pathogen interaction remain largely unknown. In this study, we explored the relevance of type-I interferons (IFNs-I) pathway using both in vitro and in vivo models of VVC. Our quantitative proteomic analysis revealed that C. albicans induces the activation of the IFNs-I pathway in human epithelial cells (ECs) of the female genital tract shortly after exposure to the fungus. Additionally, we identified β-glucans as a crucial fungal component involved in triggering this pathway. Using a VVC model in IFN-α/β receptor-deficient (Ifnar1-/-) mice, we demonstrated that IFNs-I regulate the fungal burden, C. albicans epithelial invasion, polymorphonuclear neutrophils (PMNs) recruitment, inflammatory tissue response, local cytokine balance, and the composition of T cell subsets in the draining lymph nodes. These findings underscore the pivotal role of the IFNs-I pathway in ECs-mediated responses against C. albicans, especially in the early stages of VVC development, offering insights into potential therapeutic targets for this condition.

Candida albicans is the primary agent of acute vulvovaginal candidiasis (VVC) and its recurrent form (RVVC). Local innate immunity contributes to both defense and pathogenesis during vaginal Candida infection, where epithelial β-defensins (BD) constitute key components of the mucosal barrier. We previously reported that epithelial BD-1 expression is dynamically modulated during murine and human vaginitis, revealing strain-dependent and stimulus-specific regulation but leaving the host pathways involved unresolved. This study functionally defines the contribution of key immune pathways to epithelial antimicrobial peptide regulation. Using a murine model of VVC and the virulent C. albicans strain SC5314, we aimed to evaluate the immune signaling pathways governing the temporal regulation of epithelial BD-1 and BD-3 expression during vaginal infection. In wild-type mice, both defensins displayed a biphasic pattern: early induction followed by attenuation as infection progressed. Genetic loss-of-function approaches revealed that NLRP3/IL-1β signaling is required for early BD-1 induction, whereas IL-17RA signaling preferentially supports sustained BD-3 expression. Together, these findings establish a causal and temporal link between host immune signaling and epithelial defensin regulation and reveal a transient subversion of mucosal defenses by C. albicans. This work advances understanding of epithelial innate immunity, defining distinct temporal programs for BD-1 and BD-3 and identifying NLRP3/IL-1β and IL-17RA signaling as key pathways shaping mucosal defensin expression.

Candida albicans is the primary agent of acute vulvovaginal candidiasis(VVC) and its recurrent form(RVVC). Local innate immunity contributes to both defense and pathogenesis during vaginal Candida infection, where epithelial β-defensins(BD) constitute key components of the mucosal barrier. We previously reported that epithelial BD-1 expression is dynamically modulated during murine and human vaginitis, revealing strain-dependent and stimulus-specific regulation but leaving the host pathways involved unresolved. This study functionally defines the contribution of key immune pathways to epithelial antimicrobial peptide regulation. Using a murine model of VVC and the virulent C. albicans strain SC5314, we analyzed the temporal expression of BD-1 and extended our study to BD-3. In wild-type mice, both defensins displayed a biphasic pattern: early induction followed by attenuation as infection progressed. Genetic loss-of-function approaches revealed that NLRP3/IL-1β signaling is required for early BD-1 induction, whereas IL-17RA signaling preferentially supports sustained BD-3 expression. Together, these findings establish a causal and temporal link between host immune signaling and epithelial defensin regulation, and reveal a transient subversion of mucosal defenses by C. albicans. This work advances understanding of epithelial innate immunity, defining distinct temporal programs for BD-1 and BD-3, and identifying NLRP3/IL-1β and IL-17RA signaling as key pathways shaping mucosal defensin expression.

Introduction: Candida spp. bloodstream infection is a frequent form of mycosis with high mortality rates. Biofilm formation is a potent virulence factor for Candida albicans and Candida parapsilosis , that confers significant resistance to antifungal agents and to the innate immune response. Echinocandins such as anidulafungin are new drugs that broaden the available therapeutic arsenal for invasive fungal infection treatment. Here we evaluated the effect of anidulafungin, human-Monocytes and combined treatment on mature biofilms of clinical isolates of Candida albicans and Candida parapsilosis with different intrinsic capacity to form biofilm, and on biofilm with low (LB) and high biomass (HB). Methods: Yeasts from blood isolates were molecularly identified. Lipase and acid aspartic protease production, adhesion capacity, and ability to form biofilm were evaluated; strains were classified as Weak, Moderate or Strong biofilm forming capacity. Mature biofilm with LB and HB were incubated with anidulafungin, THP-1 cell alone or exposed to both, for 22 h. Fungal damage induced by antifungal agents and/or monocytes was determined by XTT[2,3-bis(2-methoxy-4-nitro-5-sulfophenyl) 2H-tetrazolium-5-carboxanilide] metabolic assay. Results: Our results showed that anidulafungin alone could be effective to reduce mature biofilms with LB of most of the C. parapsilosis sensu stricto isolates, independent of intrinsic BF capacity of the strain. Anidulafungin in combination with human-Monocytes was effective in biofilm with LB of C. albicans and C. parapsilosis sensu stricto clinical isolates. Conclusions: The effectiveness of ANF treatment in biofilm with LB seems to be species specific, since the antifungal agent and monocytes exhibits synergistic activity on C. albicans and C. parapsilosis sensu stricto biofilm.