Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. IMPORTANCE Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis.
ISSN: 0022-538X

hal-01390974
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974/file/Mouse%20Hepatitis%20Virus%20Infection_accepted.pdf
DOI : 10.1128/JVI.01069-16

Éditeur(s) : HAL CCSD Oldendorf/Luhe
Résumé : International audience
Non-calcifying photosynthetic anthozoans have emerged as a group that may thrive under high carbon dioxide partial pressure (pCO(2)) conditions via increased productivity. However, the physiological mechanisms underlying this potential success are unclear. Here we investigated the impact of high pCO(2) on the dissolved inorganic carbon (DIC) use in the temperate sea anemone Anemonia viridis. We assessed the impacts of long-term exposure to high pCO(2), i.e. sampling in situ natural CO2 vents (Vulcano, Italy), and short-term exposure, i.e. during a 3 wk controlled laboratory experiment. We focused on photo-physiological parameters (net photosynthesis rates, chlorophyll a content and Symbiodinium density) and on carbonic anhydrase (CA) activity, an enzyme involved in the energy-demanding process of DIC absorption. Long-term exposure to high pCO(2) had no impact on Symbiodinium density and chlorophyll a content. In contrst, short-term exposure to high pCO(2) induced a significant reduction in Symbiodinium density, which together with unchanged net photosynthesis resulted in the increase of Symbiodinium productivity per cell. Finally, in both in situ long-term and laboratory short-term exposure to high pCO(2), we observed a significant decrease in the CA activity of sea anemones, suggesting a change in DIC use (i.e. from an HCO3- to a CO2 user). This change could enable a shift in the energy budget that may increase the ability of non-calcifying photosynthetic anthozoans to cope with ocean acidification.
ISSN: 0171-8630

hal-01546163
https://hal.archives-ouvertes.fr/hal-01546163
DOI : 10.3354/meps11916

Éditeur(s) : HAL CCSD Ecological Society of America
Résumé : Although niche-based and stochastic processes, including dispersal limitation and demographic stochasticity, can each contribute to community assembly, it is difficult to quantify the relative importance of each process in natural vegetation. Here, we extend Shipley's maxent model (Community Assembly by Trait Selection, CATS) for the prediction of relative abundances to incorporate both trait-based filtering and dispersal limitation from the larger landscape and develop a statistical decomposition of the proportions of the total information content of relative abundances in local communities that are attributable to trait-based filtering, dispersal limitation, and demographic stochasticity. We apply the method to tree communities in a mature, species-rich, tropical forest in French Guiana at 1-, 0.25- and 0.04-ha scales. Trait data consisted of species' means of 17 functional traits measured over both the entire meta-community and separately in each of nine 1-ha plots. Trait means calculated separately for each site always gave better predictions. There was clear evidence of trait-based filtering at all spatial scales. Trait-based filtering was the most important process at the 1-ha scale (34%), whereas demographic stochasticity was the most important at smaller scales (37-53%). Dispersal limitation from the meta-community was less important and approximately constant across scales (similar to 9%), and there was also an unresolved association between site-specific traits and meta-community relative abundances. Our method allows one to quantify the relative importance of local niche-based and meta-community processes and demographic stochasticity during community assembly across spatial and temporal scales.
ISSN: 0012-9658

hal-01032424
https://hal.archives-ouvertes.fr/hal-01032424

Éditeur(s) : HAL CCSD Royal Society, The
Résumé : International audience
Since its original description as a chordate, the Late Devonian Scaumenella mesacanthi has been interpreted alternately as a prochordate, a larval ostracoderm and an immature acanthodian. For the past 30 years, these minute specimens were generally considered as decayed acanthodians, most of them belonging to Triazeugacanthus affinis. Among the abundant material of `Scaumenella', we identified a size series of 188 specimens of Triazeugacanthus based on otolith characteristics. Despite taphonomic alteration, we describe proportional growth and progressive appearance of skeletal elements through size increase. Three ontogenetic stages are identified based on squamation extent, ossification completion and allometric growth. We demonstrate that what has been interpreted previously as various degrees of decomposition corresponds to ontogenetic changes.
ISSN: 1744-9561

hal-01545474
https://hal.archives-ouvertes.fr/hal-01545474
DOI : 10.1098/rsbl.2014.0950

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: The Ras/Raf/MEK/ERK signaling pathway is involved in essential cell processes and it is abnormally activated in similar to 30 % of cancers and cognitive disorders. Two ERK isoforms have been described, ERK1 and ERK2; ERK2 being regarded by many as essential due to the embryonic lethality of ERK2 knock-out mice, whereas mice lacking ERK1 are viable and fertile. The controversial question of why we have two ERKs and whether they have differential functions or display functional redundancy has not yet been resolved. Results: To investigate this question we used a novel approach based on comparing the evolution of ERK isoforms' sequences and protein expression across vertebrates. We gathered and cloned erk1 and erk2 coding sequences and we examined protein expression of isoforms in brain extracts in all major clades of vertebrate evolution. For the first time, we measured each isoforms' relative protein level in phylogenetically distant animals using anti-phospho antibodies targeting active ERKs. We demonstrate that squamates (lizards, snakes and geckos), despite having both genes, do not express ERK2 protein whereas other tetrapods either do not express ERK1 protein or have lost the erk1 gene. To demonstrate the unexpected squamates' lack of ERK2 expression, we targeted each ERK isoform in lizard primary fibroblasts by specific siRNA-mediated knockdown. We also found that undetectable expression of ERK2 in lizard is compensated by a greater strength of lizard's erk1 promoter. Finally, phylogenetic analysis revealed that ERK1 amino acids sequences evolve faster than ERK2' s likely due to genomic factors, including a large difference in gene size, rather than from functional differences since amino acids essential for function are kept invariant. Conclusions: ERK isoforms appeared by a single gene duplication at the onset of vertebrate evolution at least 400 Mya. Our results demonstrate that tetrapods can live by expressing either one or both ERK isoforms, supporting the notion that ERK1/2 act interchangeably. Substrate recognition sites and catalytic cleft are nearly invariant in all vertebrate ERKs further suggesting functional redundancy. We suggest that future ERK research should shift towards understanding the role and regulation of total ERK quantity, especially in light of newly described erk2 gene amplification identified in tumors.
ISSN: 1471-2148

hal-01546165
https://hal.archives-ouvertes.fr/hal-01546165
DOI : 10.1186/s12862-015-0450-x

Éditeur(s) : HAL CCSD
Résumé : International audience
Viral replication in the liver is generally detected by cellular endosomal Toll-like receptors (TLRs) and cytosolic helicase sensors that trigger antiviral inflammatory responses. Recent evidence suggests that surface TLR2 may also contribute to viral detection through recognition of viral coat proteins but its role in the outcome of acute viral infection remains elusive. In this study, we examined in vivo the role of TLR2 in acute infections induced by the highly hepatotrophic mouse hepatitis virus (MHV) type 3 and weakly hepatotrophic MHV-A59 serotype. To address this, C57BL/6 (wild-type; WT) and TLR2 knockout (KO) groups of mice were intraperitoneally infected with MHV3 or MHV-A59. MHV3 infection provoked a fulminant hepatitis in WT mice, characterized by early mortality and high alanine and aspartate transaminase levels, histopathological lesions and viral replication whereas infection of TLR2 KO mice was markedly less severe. MHV-A59 provoked a comparable mild and subclinical hepatitis in WT and TLR2 KO mice. MHV3-induced fulminant hepatitis in WT mice correlated with higher hepatic expression of interferon-β, interleukin-6, tumour necrosis factor-α, CXCL1, CCL2, CXCL10 and alarmin (interleukin-33) than in MHV-A59-infected WT mice and in MHV3-infected TLR2 KO mice. Intrahepatic recruited neutrophils, natural killer cells, natural killer T cells or macrophages rapidly decreased in MHV3-infected WT mice whereas they were sustained in MHV-A59-infected WT mice and MHV3-infected TLR2 KO. MHV3 in vitro infection of macrophagic cells induced rapid and higher viral replication and/or interleukin-6 induction in comparison to MHV-A59, and depended on viral activation of TLR2 and p38 mitogen-activated protein kinase. Taken together, these results support a new aggravating inflammatory role for TLR2 in MHV3-induced acute fulminant hepatitis. © 2016 John Wiley & Sons Ltd
Immunology

Droits : info:eu-repo/semantics/OpenAccess
hal-01373946
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01373946
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01373946/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01373946/file/Toll-like%20receptor%20%28tlr%29-2%20exacerbates%20murine%20acute%20viral%20hepatitis.pdf
DOI : 10.1111/imm.12627