2 resultados para Casey
em Biblioteca Digital da Produção Intelectual da Universidade de São Paulo (BDPI/USP)
Resumo:
Hydroidolina is a group of hydrozoans that includes Anthoathecata, Leptothecata and Siphonophorae. Previous phylogenetic analyses show strong support for Hydroidolina monophyly, but the relationships between and within its subgroups remain uncertain. In an effort to further clarify hydroidolinan relationships, we performed phylogenetic analyses on 97 hydroidolinan taxa, using DNA sequences from partial mitochondrial 16S rDNA, nearly complete nuclear 18S rDNA and nearly complete nuclear 28S rDNA. Our findings are consistent with previous analyses that support monophyly of Siphonophorae and Leptothecata and do not support monophyly of Anthoathecata nor its component subgroups, Filifera and Capitata. Instead, within Anthoathecata, we find support for four separate filiferan clades and two separate capitate clades (Aplanulata and Capitata sensu stricto). Our data however, lack any substantive support for discerning relationships between these eight distinct hydroidolinan clades.
Resumo:
Candida albicans is the most common opportunistic fungal pathogen and causes local and systemic disease in immunocompromised patients. Alveolar macrophages (AMs) are pivotal for the clearance of C. albicans from the lung. Activated AMs secrete 5-lipoxygenase-derived leukotrienes (LTs), which in turn enhance phagocytosis and microbicidal activity against a diverse array of pathogens. Our aim was to investigate the role of LTB(4) and LTD(4) in AM antimicrobial functions against C. albicans and the signaling pathways involved. Pharmacologic and genetic inhibition of LT biosynthesis as well as receptor antagonism reduced phagocytosis of C. albicans when compared with untreated or WT controls. Conversely, exogenous LTs of both classes augmented base-line C. albicans phagocytosis by AMs. Although LTB(4) enhanced mainly mannose receptor-dependent fungal ingestion, LTD(4) enhanced mainly dectin-1 receptor-mediated phagocytosis. LT enhancement of yeast ingestion was dependent on protein kinase C-delta (PKC delta) and PI3K but not PKC alpha and MAPK activation. Both LTs reduced activation of cofilin-1, whereas they enhanced total cellular F-actin; however, LTB(4) accomplished this through the activation of LIM kinases (LIMKs) 1 and 2, whereas LTD(4) did so exclusively via LIMK-2. Finally, both exogenous LTB(4) and LTD(4) enhanced AM fungicidal activity in an NADPH oxidase-dependent manner. Our data identify LTB(4) and LTD(4) as key mediators of innate immunity against C. albicans, which act by both distinct and conserved signaling mechanisms to enhance multiple antimicrobial functions of AMs.