Involvement of neutrophil hyporesponse and the role of Toll-like receptors in human immunodeficiency virus 1 protection

Autor: Silvio Urcuqui-Inchima, Stéphane Paul, Diana M. Giraldo, Juan C. Hernandez
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Lipopolysaccharides
Male
Neutrophils
medicine.medical_treatment
lcsh:Medicine
HIV Infections
Semicarbazides/chemistry
lcsh:Science
Lymphotoxin-alpha
Paracoccidioides/drug effects
Expressed Sequence Tags
Terpenes/pharmacology
Toll-like receptor
Multidisciplinary
Pattern recognition receptor
virus diseases
Middle Aged
Cytokine
Oligodeoxyribonucleotides
Host-Pathogen Interactions
Tumor necrosis factor alpha
Female
medicine.symptom
Research Article
Signal Transduction
Adult
Primary Cell Culture
Inflammation
Biology
Lipopeptides
Adjuvants
Immunologic
medicine
Gene Expression Regulation
Fungal/genetics
Humans
RNA
Messenger
Interleukin 6
Innate immune system
Antifungal Agents/chemistry
Tumor Necrosis Factor-alpha
Interleukins
lcsh:R
Virion
Immunity
Innate
Toll-Like Receptor 2
Toll-Like Receptor 4
TLR2
Gene Expression Regulation
Case-Control Studies
Toll-Like Receptor 9
Immunology
biology.protein
HIV-1
lcsh:Q
Reactive Oxygen Species
Zdroj: PLoS ONE, Vol 10, Iss 3, p e0119844 (2015)
Repositorio UdeA
Universidad de Antioquia
instacron:Universidad de Antioquia
PLoS ONE
ISSN: 1932-6203
Popis: ABSTARCT: Paracoccidioidomycosis (PCM) is a systemic granulomatous human mycosis caused by fungi of the genus Paracoccidioides, which is geographically restricted to Latin America. Inhalation of spores, the infectious particles of the fungus, is a common route of infection. The PCM treatment of choice is azoles such as itraconazole, but sulfonamides and amphotericin B are used in some cases despite their toxicity to mammalian cells. The current availability of treatments highlights the need to identify and characterize novel targets for antifungal treatment of PCM as well as the need to search for new antifungal compounds obtained from natural sources or by chemical synthesis. To this end, we evaluated the antifungal activity of a camphene thiosemicarbazide derivative (TSC-C) compound on Paracoccidioides yeast. To determine the response of Paracoccidioides spp. to TSC-C, we analyzed the transcriptional profile of the fungus after 8 h of contact with the compound. The results demonstrate that Paracoccidioides lutzii induced the expression of genes related to metabolism; cell cycle and DNA processing; biogenesis of cellular components; cell transduction/signal; cell rescue, defense and virulence; cellular transport, transport facilities and transport routes; energy; protein synthesis; protein fate; transcription; and other proteins without classification. Additionally, we observed intensely inhibited genes related to protein synthesis. Analysis by fluorescence microscopy and flow cytometry revealed that the compound induced the production of reactive oxygen species. Using an isolate with down-regulated SOD1 gene expression (SOD1-aRNA), we sought to determine the function of this gene in the defense of Paracoccidioides yeast cells against the compound. Mutant cells were more susceptible to TSC-C, demonstrating the importance of this gene in response to the compound. The results presented herein suggest that TSC-C is a promising candidate for PCM treatment.
Databáze: OpenAIRE
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