19 research outputs found
Etude de l'expression et du rôle de molécules solubles de l'inflammation, la chimiokine CXCL14 et la protéine IL-18bp, dans le contexte des hépatites virales : nouveaux biomarqueurs et cibles thérapeutiques
No full textViral hepatitis is the most common form of hepatitis, with more than 360 million cases worldwide. Viral infection leads to the mobilization of the immune response via cytokines production, in particular chemokines and interleukins. The first part of our work focused on studying the role of the IL-18bp protein. For this, a model of murine hepatitis fulminant by inoculation of the murine hepatitis virus (MHV-3) was developed in wild-type mice and mice deficient in the protein IL-18bp. Following infection, we demonstrated that IL-18bp protein did not affect the development of fulminant hepatitis in mice. The second part of our work focused on the study of the chemokine CXCL14. We have demonstrated that this chemokine is expressed and then released by the hepatocytes during their lysis induced by viral infection. Our study also demonstrated that chemokine is present in high concentrations in the serum of patients with acute viral hepatitis. The MHV-3- induced viral hepatitis model was developed in wildtype mice and mice deficient in CXCL14. Infection of these mice with MHV-3 did not demonstrate a specific role for the chemokine CXCL14. However, differences in the immune response in uninfected mice have demonstrated a role for CXCL14 in immune surveillance. In fact, mice deficient in CXCL14 demonstrate a more active immune activity mediated by B lymphocytes than that observed in wild-type mice. The chemokine CXCL14 would therefore be a central actor in the immune response.Les hépatites virales constituent la forme la plus fréquente d’hépatite, avec plus de 360 millions de cas dans le Monde. L’infection virale entraine la mobilisation de la réponse immunitaire via la production de cytokines, en particulier de chimiokines et d’interleukines. Une première partie de nos travaux a porté sur l’étude du rôle de la protéine IL-18bp. Pour cela, un modèle d’hépatite murine virale fulminante par l’inoculation du virus de l’hépatite murine (MHV-3) a été développé chez des souris sauvages et des souris déficientes pour la protéine IL-18bp. Suite à l’infection, nous avons mis en évidence que la protéine IL-18bp n’impactait pas le développement de l’hépatite fulminante chez la souris. La seconde partie de nos travaux a porté sur l’étude de la chimiokine CXCL14. Nous avons mis en évidence que cette chimiokine était exprimée puis relarguée par les hépatocytes lors de leur lyse induite par l’infection virale. Notre étude a également démontré que la chimiokine était présente à de fortes concentrations dans le sérum de patients présentant une hépatite aiguë d’origine virale. Le modèle d’hépatite virale induite par le MHV-3 a été développé chez des souris sauvages et des souris déficientes pour CXCL14. L’infection de ces souris par le MHV-3 n’a pas démontré de rôle spécifique de la chimiokine CXCL14. Cependant, des différences de réponse immunitaire chez les souris non infectées ont mis en évidence un rôle de CXCL14 dans la surveillance immunitaire. En effet, les souris déficientes pour CXCL14 démontrent une activité immunitaire médiée par les lymphocytes B plus active que celle observée chez les souris sauvages. La chimiokine CXCL14 serait donc un acteur central de la réponse immunitaire
Etude de l'expression et du rôle de molécules solubles de l'inflammation, la chimiokine CXCL14 et la protéine IL-18bp, dans le contexte des hépatites virales : nouveaux biomarqueurs et cibles thérapeutiques
No full textViral hepatitis is the most common form of hepatitis, with more than 360 million cases worldwide. Viral infection leads to the mobilization of the immune response via cytokines production, in particular chemokines and interleukins. The first part of our work focused on studying the role of the IL-18bp protein. For this, a model of murine hepatitis fulminant by inoculation of the murine hepatitis virus (MHV-3) was developed in wild-type mice and mice deficient in the protein IL-18bp. Following infection, we demonstrated that IL-18bp protein did not affect the development of fulminant hepatitis in mice. The second part of our work focused on the study of the chemokine CXCL14. We have demonstrated that this chemokine is expressed and then released by the hepatocytes during their lysis induced by viral infection. Our study also demonstrated that chemokine is present in high concentrations in the serum of patients with acute viral hepatitis. The MHV-3- induced viral hepatitis model was developed in wildtype mice and mice deficient in CXCL14. Infection of these mice with MHV-3 did not demonstrate a specific role for the chemokine CXCL14. However, differences in the immune response in uninfected mice have demonstrated a role for CXCL14 in immune surveillance. In fact, mice deficient in CXCL14 demonstrate a more active immune activity mediated by B lymphocytes than that observed in wild-type mice. The chemokine CXCL14 would therefore be a central actor in the immune response.Les hépatites virales constituent la forme la plus fréquente d’hépatite, avec plus de 360 millions de cas dans le Monde. L’infection virale entraine la mobilisation de la réponse immunitaire via la production de cytokines, en particulier de chimiokines et d’interleukines. Une première partie de nos travaux a porté sur l’étude du rôle de la protéine IL-18bp. Pour cela, un modèle d’hépatite murine virale fulminante par l’inoculation du virus de l’hépatite murine (MHV-3) a été développé chez des souris sauvages et des souris déficientes pour la protéine IL-18bp. Suite à l’infection, nous avons mis en évidence que la protéine IL-18bp n’impactait pas le développement de l’hépatite fulminante chez la souris. La seconde partie de nos travaux a porté sur l’étude de la chimiokine CXCL14. Nous avons mis en évidence que cette chimiokine était exprimée puis relarguée par les hépatocytes lors de leur lyse induite par l’infection virale. Notre étude a également démontré que la chimiokine était présente à de fortes concentrations dans le sérum de patients présentant une hépatite aiguë d’origine virale. Le modèle d’hépatite virale induite par le MHV-3 a été développé chez des souris sauvages et des souris déficientes pour CXCL14. L’infection de ces souris par le MHV-3 n’a pas démontré de rôle spécifique de la chimiokine CXCL14. Cependant, des différences de réponse immunitaire chez les souris non infectées ont mis en évidence un rôle de CXCL14 dans la surveillance immunitaire. En effet, les souris déficientes pour CXCL14 démontrent une activité immunitaire médiée par les lymphocytes B plus active que celle observée chez les souris sauvages. La chimiokine CXCL14 serait donc un acteur central de la réponse immunitaire
Study of expression and function of solube molecules of inflammation, the CXCL14 chemokine and the IL-18 binding protein, during viral hepatitis : new biomarkers and therapeutic targets
No full textLes hépatites virales constituent la forme la plus fréquente d’hépatite, avec plus de 360 millions de cas dans le Monde. L’infection virale entraine la mobilisation de la réponse immunitaire via la production de cytokines, en particulier de chimiokines et d’interleukines. Une première partie de nos travaux a porté sur l’étude du rôle de la protéine IL-18bp. Pour cela, un modèle d’hépatite murine virale fulminante par l’inoculation du virus de l’hépatite murine (MHV-3) a été développé chez des souris sauvages et des souris déficientes pour la protéine IL-18bp. Suite à l’infection, nous avons mis en évidence que la protéine IL-18bp n’impactait pas le développement de l’hépatite fulminante chez la souris. La seconde partie de nos travaux a porté sur l’étude de la chimiokine CXCL14. Nous avons mis en évidence que cette chimiokine était exprimée puis relarguée par les hépatocytes lors de leur lyse induite par l’infection virale. Notre étude a également démontré que la chimiokine était présente à de fortes concentrations dans le sérum de patients présentant une hépatite aiguë d’origine virale. Le modèle d’hépatite virale induite par le MHV-3 a été développé chez des souris sauvages et des souris déficientes pour CXCL14. L’infection de ces souris par le MHV-3 n’a pas démontré de rôle spécifique de la chimiokine CXCL14. Cependant, des différences de réponse immunitaire chez les souris non infectées ont mis en évidence un rôle de CXCL14 dans la surveillance immunitaire. En effet, les souris déficientes pour CXCL14 démontrent une activité immunitaire médiée par les lymphocytes B plus active que celle observée chez les souris sauvages. La chimiokine CXCL14 serait donc un acteur central de la réponse immunitaire.Viral hepatitis is the most common form of hepatitis, with more than 360 million cases worldwide. Viral infection leads to the mobilization of the immune response via cytokines production, in particular chemokines and interleukins. The first part of our work focused on studying the role of the IL-18bp protein. For this, a model of murine hepatitis fulminant by inoculation of the murine hepatitis virus (MHV-3) was developed in wild-type mice and mice deficient in the protein IL-18bp. Following infection, we demonstrated that IL-18bp protein did not affect the development of fulminant hepatitis in mice. The second part of our work focused on the study of the chemokine CXCL14. We have demonstrated that this chemokine is expressed and then released by the hepatocytes during their lysis induced by viral infection. Our study also demonstrated that chemokine is present in high concentrations in the serum of patients with acute viral hepatitis. The MHV-3- induced viral hepatitis model was developed in wildtype mice and mice deficient in CXCL14. Infection of these mice with MHV-3 did not demonstrate a specific role for the chemokine CXCL14. However, differences in the immune response in uninfected mice have demonstrated a role for CXCL14 in immune surveillance. In fact, mice deficient in CXCL14 demonstrate a more active immune activity mediated by B lymphocytes than that observed in wild-type mice. The chemokine CXCL14 would therefore be a central actor in the immune response
Optimized intramuscular immunization with VSV-vectored spike protein triggers a superior immune response to SARS-CoV-2.
No full textImmunization with vesicular stomatitis virus (VSV)-vectored COVID-19 vaccine candidates expressing the SARS-CoV-2 spike protein in place of the VSV glycoprotein relies implicitly on expression of the ACE2 receptor at the muscular injection site. Here, we report that such a viral vector vaccine did not induce protective immunity following intramuscular immunization of K18-hACE2 transgenic mice. However, when the viral vector was trans-complemented with the VSV glycoprotein, intramuscular immunization resulted in high titers of spike-specific neutralizing antibodies. The vaccinated animals were fully protected following infection with a lethal dose of SARS-CoV-2-SD614G via the nasal route, and partially protected if challenged with the SARS-CoV-2Delta variant. While dissemination of the challenge virus to the brain was completely inhibited, replication in the lung with consequent lung pathology was not entirely controlled. Thus, intramuscular immunization was clearly enhanced by trans-complementation of the VSV-vectored vaccines by the VSV glycoprotein and led to protection from COVID-19, although not achieving sterilizing immunity
Neutrophil proteases are protective against SARS-CoV-2 by degrading the spike protein and dampening virus-mediated inflammation.
No full textStudies on severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have highlighted the crucial role of host proteases for viral replication and the immune response. The serine proteases furin and TMPRSS2 and lysosomal cysteine proteases were shown to facilitate virus entry by limited proteolytic processing of the spike (S) protein. While neutrophils are recruited to the lungs during COVID-19 pneumonia, little is known about the role of the neutrophil serine proteases (NSPs) cathepsin G (CatG), elastase (NE), and proteinase 3 (PR3) on SARS-CoV-2 entry and replication. Furthermore, the current paradigm is that NSPs may contribute to the pathogenesis of severe COVID-19. Here, we show that these proteases cleave the S protein at multiple sites and abrogate virus entry and replication in vitro. In mouse models, CatG significantly inhibited viral replication in the lung. Importantly, lung inflammation and pathology were increased in mice deficient in NE and/or CatG. These results reveal that NSPs contribute to innate defenses against SARS-CoV-2 infection via proteolytic inactivation of the S protein and that NE and CatG limit lung inflammation in vivo. We conclude that therapeutic interventions aiming to reduce the activity of NSPs may interfere with virus clearance and inflammation in COVID-19 patients
The anti-fibrotic role of mast cells in the liver is mediated by HLA-G and interaction with hepatic stellate cells
No full textInternational audienceBackground & aims - We have reported a significant association between HLA-G expression or the number of hepatic mast cells and liver fibrosis. Here, we investigated the role of HLA-G and mast cells in liver fibrosis, focusing, in particular, on interactions between human mast and stellate cells. Methods - Human mast cells (HMC cell line, CD34-derived mast cells, or tissue-derived mast cells) were co-cultured with purified human hepatic stellate cells (HSCs), and collagen I production by HSCs was evaluated. Mast cells and HSCs were characterized by immunocytochemistry. Various conditions were tested: different times in direct or indirect contact, presence or absence of cytokines, addition or not of HLA-G, and presence or absence of specific protease inhibitors. Results - The reciprocal interaction between HSCs and mast cells led to the attraction of mast cells to HSCs in vivo and in vitro, and to a significant decrease in collagen production, at all times of co-culture, following the direct or indirect contact of mast cells with HSCs alone or in the presence of TGF-β, IFN-α or IL-10. We identified the diffusible factors involved in collagen I degradation as mast cell proteases. Moreover, HLA-G expression increased during the co-culture of HSCs and mast cells, with HLA-G acting on both mast cells and HSCs, to enhance collagen I degradation. Conclusions - Mast cells play a beneficial, anti-fibrotic role in liver fibrosis, via the HLA-G-mediated decrease of collagen I. These findings are consistent with high levels of cross-communication between mast cells and hepatic stellate cells and the role of HLA-G
Influence of the calendering step on the adhesion properties of coextruded structures
No full textCopyright 2012 Carl Hanser Verlag. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the Carl Hanser Verlag. The authors are grateful to the publisher, Carl Hanser Verlag, for letting the manuscript being archived in this Open Access repository. The final publication is available at http://www.polymer-process.com/IPP2516International audienceThe coupled coextrusion calendering process of multilayer thermoplastic sheets has been studied. The structure of the film has been observed, the density of chemical links at the interface and the adhesion between the coextruded layers have been measured. There are some controversial features about the influence of calendering parameters. Several models of increasing complexity are proposed to master the process and its influence on adhesion. A multilayer thermal model accounting for the crystallization kinetics of both polymers allows defining qualitatively the temperature field especially at the interface between the two layers. A multilayer thermo- mechanical model provides quantitative figures on the stress, shear, elongation and temperature fields in the coextruded film and especially at the interface. Relationships between these parameters, density of chemical links at the interface, crystalline structure of the sample and peeling forces are discussed
Circulating levels of CXCL11 and CXCL12 are biomarkers of cirrhosis in patients with chronic hepatitis C infection
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Serum CXCL10, CXCL11, CXCL12, and CXCL14 chemokine patterns in patients with acute liver injury
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CXCL14 Chemokine Exacerbates Acute Viral Hepatitis in Coronavirus MHV-Infected Mice and Is Associated With Human Acute Viral Hepatitis
No full textInternational audienceDeaths from viral hepatitis continue to rise around the world due to the lack of early biomarkers. We aimed here to evaluate the chemokine CXCL14, as a novel biomarker in acute viral hepatitis. We used a mouse model of acute hepatitis induced by murine hepatitis virus (MHV), a hepatotropic and lytic coronavirus, and showed that CXCL14 is overexpressed in the liver and sera of infected mice. Using primary cultures of murine and human hepatocytes, we showed that hepatocytes are the main source of CXCL14 after lytic hepatotropic virus infection and that CXCL14 expression is also induced by the pro-inflammatory cytokines IL-6 and TNF alpha. CXCL14 KO mice infected with MHV were partially protected and showed an attenuated antiviral immune response compared to wild-type mice. Finally, we show that CXCL14 is overexpressed in the sera of human patients infected with hepatitis viruses A, B, and E or herpes simplex virus. A positive correlation between CXCL14 and ALT levels in the sera of patients with acute herpetic hepatitis, as well as in mice models, suggests that hepatocyte lysis is necessary for the release of CXCL14. Overall, these data highlight that CXCL14 expression is associated with the occurrence of acute viral hepatitis and could be considered an alarmin and a new indicator of inflammation. CXCL14 serum levels are also associated with the severity of viral-induced liver injury
