IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells.

Interleukin 17 (IL-17)-mediated immunity plays a key role in protection from fungal infections in mice and man. Here, we confirmed that mice deficient in the IL-17 receptor or lacking the ability to secrete IL-17 are highly susceptible to systemic candidiasis, but we found that temporary blockade of the IL-17 pathway during infection in wild-type mice did not impact fungal control. Rather, mice lacking IL-17 receptor signaling had a cell-intrinsic impairment in the development of functional NK cells, which accounted for the susceptibility of these mice to systemic fungal infection. NK cells promoted antifungal immunity by secreting GM-CSF, necessary for the fungicidal activity of neutrophils. These data reveal that NK cells are crucial for antifungal defense and indicate a role for IL-17 family cytokines in NK cell development. The IL-17-NK cell axis may impact immunity against not only fungi but also bacteria, viruses, and tumors.

Correction: Syk Signaling in Dendritic Cells Orchestrates Innate Resistance to Systemic Fungal Infection.

[This corrects the article DOI: 10.1371/journal.ppat.1004276.].

Syk signaling in dendritic cells orchestrates innate resistance to systemic fungal infection.

Host protection from fungal infection is thought to ensue in part from the activity of Syk-coupled C-type lectin receptors and MyD88-coupled toll-like receptors in myeloid cells, including neutrophils, macrophages and dendritic cells (DCs). Given the multitude of cell types and receptors involved, elimination of a single pathway for fungal recognition in a cell type such as DCs, primarily known for their ability to prime T cell responses, would be expected to have little effect on innate resistance to fungal infection. Here we report that this is surprisingly not the case and that selective loss of Syk but not MyD88 in DCs abrogates innate resistance to acute systemic Candida albicans infection in mice. We show that Syk expression by DCs is necessary for IL-23p19 production in response to C. albicans, which is essential to transiently induce GM-CSF secretion by NK cells that are recruited to the site of fungal replication. NK cell-derived-GM-CSF in turn sustains the anti-microbial activity of neutrophils, the main fungicidal effectors. Thus, the activity of a single kinase in a single myeloid cell type orchestrates a complex series of molecular and cellular events that underlies innate resistance to fungal sepsis.

A novel Th cell epitope of Candida albicans mediates protection from fungal infection.

Fungal pathogens are a frequent cause of opportunistic infections. They live as commensals in healthy individuals but can cause disease when the immune status of the host is altered. T lymphocytes play a critical role in pathogen control. However, specific Ags determining the activation and function of antifungal T cells remain largely unknown. By using an immunoproteomic approach, we have identified for the first time, to our knowledge, a natural T cell epitope from Candida albicans. Isolation and sequencing of MHC class II-bound ligands from infected dendritic cells revealed a peptide that was recognized by a major population of all Candida-specific Th cells isolated from infected mice. Importantly, human Th cells also responded to stimulation with the peptide in an HLA-dependent manner but without restriction to any particular HLA class II allele. Immunization of mice with the peptide resulted in a population of epitope-specific Th cells that reacted not only with C. albicans but also with other clinically highly relevant species of Candida including the distantly related Candida glabrata. The extent of the reaction to different Candida species correlated with their degree of phylogenetic relationship to C. albicans. Finally, we show that the newly identified peptide acts as an efficient vaccine when used in combination with an adjuvant inducing IL-17A secretion from peptide-specific T cells. Immunized mice were protected from fatal candidiasis. Together, these results uncover a new immune determinant of the host response against Candida ssp. that could be exploited for the development of antifungal vaccines and immunotherapies.

Identifying priority areas for conservation in mexican tropical deciduous forest based on tree species

El objetivo principal del trabajo fue identificar y jerarquizar áreas prioritarias para la conservación de los árboles que se distribuyen de manera exclusiva o casi exclusivamente en el bosque tropical caducifolio en México, un tipo de vegetación seriamente amenazado a nivel mundial. La información se obtuvo a través de la consulta de literatura florística especializada, con la que se generó una lista de 425 especies arbóreas (67,5 por ciento endémicas de México), con 56 familias y 185 géneros registrados a nivel de estado. El grado de conservación de las especies se evaluó registrando su presencia en las Áreas Naturales Protegidas de México que incluyen dentro de sus límites porciones con bosque tropical caducifolio. Por análisis de parsimonia se determinaron 16 áreas de endemismo, sustentadas por 54 sinapomorfias y 73 autapomorfias (72,4 por ciento endémicas de México). Las áreas protegidas incluyen una baja a mediana proporción de las especies arbóreas de amplia distribución (129 especies, 30,3 por ciento) y de aquellas que caracterizan las áreas de endemismo (56 de 127 especies, 44,1 por ciento). En este último grupo, solo 7 especies están incluidas en una categoria de riesgo. El análisis de complementaridad (basado en la riqueza de especies y de aquellas localizadas en áreas de endemismo) y de diversidad filogenética (número de familias y géneros encontrados en cada estado) coinciden en asignar como áreas prioritarias para la conservación a los estados de Chiapas, Guerrero, Jalisco, Michoacán, Oaxaca y Yucatán. Con base en los resultados se proponen recomendaciones para el desarrollo de estrategias para asegurar la conservación de los árboles del bosque tropical caducifolio mexicano