Fungal skin infections significantly contribute to the global human disease burden, yet our understanding of cutaneous immunity against dermatophytes remains limited. Previously, we developed a model of epicutaneous infection with Microsporum canis in C57BL/6 mice, which highlighted the critical role of IL-17RA signaling in antidermatophyte defenses. In this study, we expanded our investigation to the human pathogen Nannizzia gypsea and demonstrated that skin yBTCRint and CD8/CD4 double-negative (3TCR+ T cells are the principal producers of IL-17A during dermatophytosis. These IL-17A+ T cells exhibited an activated/memory phenotype, including a subset of proliferating tissue-resident cells. Notably, restriction of lymphocyte trafficking after fingolimod administration in infected mice did not lead to increased susceptibility, indicating that local antifungal defenses are independent of T-cell priming in lymph nodes. In addition, Rag1-/- mice lacking T and B lymphocytes effectively controlled infection and exhibited increased IL-17A production by innate lymphoid cells. Furthermore, Rag2-/-Il2rg-/- mice, devoid of T, B, and innate lymphoid cells, were highly susceptible to dermatophytosis compared with Rag2-/-or wild-type mice, demonstrating that innate lymphoid cells are sufficient to antifungal defenses in T-cell-deficient mice. In conclusion, our study underscores the coordinated interplay between skin yBT, a(3T, and innate lymphoid cell subsets in controlling primary N gypsea dermatophytosis.
We report a case of Enterocytozoon bieneusi infection in a pediatric hematopoietic stem cell transplant recipient in Argentina. Spores were visualized in feces using Calcofluor White and modified trichrome stainings. PCR and sequencing identified E. bieneusi genotype D in fecal samples and liver samples, confirming extraintestinal dissemination of the parasite.
Lung dendritic cells (DC) are powerful antigen-presenting cells constituted by various subpopulations that differ in terms of their function and origin and differentially regulate cell-mediated antifungal immunity. The lung is the primary target organ of Cryptococcus neoformans and C. gattii infections, which makes it essential in the establishment of the first line of anti-cryptococcal defense. However, the lung-specific dynamics and function of DC subsets are poorly understood in cryptococcosis. In this study, we provide evidence for the in vivo function of a conventional langerin-expressing DC1 dendritic cell (LangDC1) population during the first week of intratracheal C. neoformans infection in mice. By using conditional depletion of LangDC1 after diphtheria toxin treatment of LangDTREGFP mice, we demonstrate that these animals better control the fungal infection and produce type 1 and 17 cytokines in the context of a type 2 immune response, favoring a predominance of iNOS over arginase-1 expression by pulmonary cells. Our results suggest that LangDC1 cells play a role in impairing immune response for the clearance of C. neoformans in the early stage of pulmonary infection.
Dermatophytoses (ringworms) are among the most frequent skin infections and are a highly prevalent cause of human disease worldwide. Despite the incidence of these superficial mycoses in healthy people and the compelling evidence on chronic and deep infections in immunocompromised individuals, the mechanisms controlling dermatophyte invasion in the skin are scarcely known. In the last years, the association between certain primary immunodeficiencies and the susceptibility to severe dermatophytosis as well as the evidence provided by novel experimental models mimicking human disease have significantly contributed to deciphering the basic immunological mechanisms against dermatophytes. In this review, we outline the current knowledge on fungal virulence factors involved in the pathogenesis of dermatophytoses and recent evidence from human infections and experimental models that shed light on the cells and molecules involved in the antifungal cutaneous immune response. The latest highlights emphasize the contribution of C-type lectin receptors signaling and the cellular immune response mediated by IL-17 and IFN-γ in the anti-dermatophytic defense and skin inflammation control.
Microsporidia are obligate intracellular fungi with a remarkable ability to infect a wide range of invertebrate and vertebrate hosts. Namely, Enterocytozoon bieneusi is the most frequently microsporidia reported worldwide, and mainly associated with chronic diarrhea and wasting syndrome in AIDS patients. Microscopy and PCR-based detection techniques are effective for diagnosis and identification of species and genotypes; however, these methods should be standardized in each laboratory. In this study, we performed microscopy and nested PCR techniques with PCR product sequencing to detect E. bieneusi in human stool samples. These techniques, if applied together, might prove useful for diagnosis and future epidemiological studies of intestinal microsporidiosis in Argentina.
Despite worldwide prevalence of superficial mycoses, the immune response in dermatophytosis has scarcely been investigated. In this study, we developed a model of superficial skin infection in C57BL/6 mice with Microsporum canis, a highly prevalent human pathogen. This model mimics mild inflammatory human dermatophytosis, characterized by neutrophil recruitment and fungal invasion limited to the epidermis and exhibits the establishment of a specific T helper type 17 immune response during infection. By using IL-17RA- or IL-17A/F-deficient mice we showed that, in the absence of a functional IL-17 pathway, M. canis extensively colonizes the epidermis and promotes an exaggerated skin inflammation and a shift to an IFN-γ-mediated (T helper type 1) response. IL-17 signaling was not involved in neutrophil influx to skin or fungal invasion to deeper tissues. Finally, this study shows that skin langerin-expressing cells contribute to the antifungal T helper type 17 response in vivo. In conclusion, these data directly show a dual function of IL-17 cytokines in dermatophytosis by controlling superficial infection and down-modulating a T helper type 1 antifungal response.
Fasciolosis is a zoonotic disease of increasing importance due to its worldwide distribution and elevated economic losses. Previously, we demonstrated that Fasciola hepatica excretory-secretory products (FhESP) induce immunomodulatory effects on peritoneal macrophages in a Dectin-1 dependent manner. In this study, we observed that peritoneal macrophages from naive BALB/c mice stimulated in vitro with FhESP presented increased expression levels of phosphorylated extracellular-signal-regulated kinase (ERK), and this effect was dependent on Syk, protein kinase C (PKC) and Dectin-1. In this sense, we observed increased levels of arginase activity, IL-10 and TGF-β in macrophages stimulated with FhESP, which were dependent on PKC and ERK. Furthermore, we observed that the increased arginase activity, as well as in TGF-β and IL-10 levels, was partially dependent on IL-10 receptor signaling in macrophages that were pre-incubated with anti-IL10R before being stimulated with FhESP. Taken together, these results suggest the participation of Dectin-1 and Syk in FhESP interaction with peritoneal macrophages and the possible role of ERK and IL-10 in downstream signaling pathways involved in the immunomodulatory effects induced by Fasciola hepatica products.
This study demonstrates the capacity of the one-step polymerase chain reaction (PCR) fingerprinting method using the microsatellite primers (GACA)4 or (GTG)5 (MSP-PCR) to identify six of the most frequent dermatophyte species causing cutaneous mycosis. PCR with (GACA)4 was a suitable method to recognise Microsporum canis, Microsporum gypseum, Trichophyton rubrum and Trichophyton interdigitale among 82 Argentinian clinical isolates, producing the most simple and reproducible band profiles. In contrast, the identification of Trichophyton mentagrophytes and Trichophyton tonsurans was achieved using PCR with (GTG)5. In this way, the sequential application of PCR using (GACA)4 and (GTG)5 allowed the successful typification of clinical isolates which had not been determined by mycological standard techniques. In this work, the intraspecies variability among 33 clinical isolates of M. canis was detected using random amplification of polymorphic DNA (RAPD-PCR) with the primers OPI-07 and OPK-20. The genetic variations in the isolates of M. canis were not associated with clinical features of lesions or pet ownership, but a geographical restriction of one genotype was determined with OPK-20, suggesting a clonal diversity related to different ecological niches in certain geographical areas. The results of this work demonstrate that the detection of intraspecies polymorphisms in M. canis by RAPD-PCR may be applied in future molecular epidemiological studies to identify endemic strains, the route of infection in an outbreak or the coexistence of different strains in a single infection.
The objective of the present investigation was to detect and characterize enteroparasites in children and adolescents of the community Los Cedros in the province of Cordoba. Parasites were detected in 111 individuals (6 months to 21 years old) by: macroscopic and microscopic examination (direct and Willis and Ritchie concentration methods) and anal swabs (Graham method). The prevalence of parasites was 74% without significant association between women and men (51% vs. 49%). Children from 5 to 11 years of age evidenced the greatest percentages of parasitosis (61%). The species identified were: Enterobius vermicularis (54%), Blastocystis hominis (52%), Giardia lamblia (28%), Entamoeba coil (17%), Endolimax nana (10%), Chilomastix mesnilii (2%), lodamoeba butschlii (2%) and Hymenolepis nana (5%). The prevalence of monoparasitosis and poliparasitosis was 44% and 56%, respectively, without any significant association with age and sex. In children and adolescents with poliparasitosis, the most frequent combinations were: Enterobius vermicularis/Blastocystis hominis and Enterobius vermicularis/Giardia lamblia. In conclusion, this study determined a high prevalence of enteropararasites in children and adolescents of this periurban community in the province of Cordoba that could help to establish and to consolidate control programs and epidemiological surveillance.
The objective of the present investigation was to detect and characterize enteroparasites in children and adolescents of the community Los Cedros in the prov...