15 research outputs found

    Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation.

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    It has been shown that γδ T cells protect against the formation of squamous cell carcinoma (SCC) in several models. However, the role of γδ T cells in human papillomavirus (HPV)-associated uterine cervical SCC, the third-leading cause of death by cancer in women, is unknown. Here, we investigated the impact of γδ T cells in a transgenic mouse model of carcinogenesis induced by HPV16 oncoproteins. Surprisingly, γδ T cells promoted the development of HPV16 oncoprotein-induced lesions. HPV16 oncoproteins induced a decrease in epidermal Skint1 expression and the associated antitumor Vγ5 <sup>+</sup> γδ T cells, which were replaced by γδ T-cell subsets (mainly Vγ6 <sup>+</sup> γδ <sup>low</sup> CCR2 <sup>+</sup> CCR6 <sup>-</sup> ) actively producing IL-17A. Consistent with a proangiogenic role, γδ T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL-17A <sup>+</sup> γδ T cells could only be observed at the cancer stage (SCC), where HPV oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16 oncoproteins induce a reorganization of the local epithelial-associated γδ T-cell subpopulations, thereby promoting angiogenesis and cancer development

    PDMS microfluidics developed for polymer based photonic biosensors

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    In this work, advances in the fabrication technology and functional analysis of a polymer microfluidic system-as a significant part of a developed polymer photonic biosensor-are reported. Robust and cost-effective microfluidics in PDMS including sample preparation functions is designed and realized by using SU-8 moulding replica. Surface modification strategies using Triton X-100 and PDMS-PEO and their effect on device sealing and non-specific protein adsorption are investigated by contact angle measurement and in situ fluorescence microscopy. © 2014 Springer-Verlag Berlin Heidelberg

    The Varicella-Zoster Virus ORF47 Kinase Interferes with Host Innate Immune Response by Inhibiting the Activation of IRF3

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    The innate immune response constitutes the first line of host defence that limits viral spread and plays an important role in the activation of adaptive immune response. Viral components are recognized by specific host pathogen recognition receptors triggering the activation of IRF3. IRF3, along with NF-κB, is a key regulator of IFN-β expression. Until now, the role of IRF3 in the activation of the innate immune response during Varicella-Zoster Virus (VZV) infection has been poorly studied. In this work, we demonstrated for the first time that VZV rapidly induces an atypical phosphorylation of IRF3 that is inhibitory since it prevents subsequent IRF3 homodimerization and induction of target genes. Using a mutant virus unable to express the viral kinase ORF47p, we demonstrated that (i) IRF3 slower-migrating form disappears; (ii) IRF3 is phosphorylated on serine 396 again and recovers the ability to form homodimers; (iii) amounts of IRF3 target genes such as IFN-β and ISG15 mRNA are greater than in cells infected with the wild-type virus; and (iv) IRF3 physically interacts with ORF47p. These data led us to hypothesize that the viral kinase ORF47p is involved in the atypical phosphorylation of IRF3 during VZV infection, which prevents its homodimerization and subsequent induction of target genes such as IFN-β and ISG15

    In Vitro Detection And Characterization Of Bacteriocin-Like Inhibitory Activity Of Lactic Acid Bacteria (Lab) Isolated From Senegalese Local Food Products

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    The prevalence of lactic acid bacteria (LAB) in Senegalese local food products was determined to be 109 CFU/g in millet flour and milk products, and 103 CFU/g in seafood products. These food products are generally preserved by spontaneous fermentation (without addition of starters). Of 220 lactic acid bacteria strains randomly selected from such products, 12 isolates capable of producing bacteriocin-like substances (bac+) were detected. Based on the use of API 50 CH test kits and 16S rDNA sequencing, 11 isolates were characterized as Lactococcus lactis subsp. lactis strains and one as an Enterococcus faecium strain. Nisin- and enterocin B-encoding genes were respectively identified in the bac+ lactococcal strains and the E. faecium strain. Since the bac+ Lc. lactis strains were isolated from different products, it suggests a high potential of growth by these strains in variable ecological environments. Expression of the nisin gene was indicated for one of the lactococcal strains, designated Lc. lactis subsp. lactis CWBI-B1410, which showed the highest in vitro antibacterial activity. An antibacterial preparation prepared from the CWBI-B1410 strain showed many similarities with nisin with regards to its inhibitory effects, heat resistance, protease sensitivity profile, as well as retention time of the antibacterial substances on a C18 column. These results suggest that a nisin-like substance is produced by the CWBI-B1410 strain. This strain has been selected for application as an additional barrier to supplementation with sodium chloride as a means to improve the bacterial quality of fish commodities in Senegal
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