Bulletin et memoires de l'Academie royale de medecine de Belgique最新文献

April 2009 saw the emergence of a pandemic strain of influenza A H1N1 in North America. The virus is now prevalent worldwide in human populations and has become a significant public health problem with substantial economic and other consequences. The virus contains a combination of genes from influenza viruses previously known to circulate in pigs, birds, and humans. The human-animal interface is known to play an important role in the emergence of pandemic influenza viruses, and animals have occasionally been infected with the pandemic H1N1 virus. There is no evidence, however, that animals are playing a significant role in the epidemiology of this current pandemic. With regards to the implications for animal health, OIE recommends enhanced surveillance for the pandemic H1N1 virus in animals so that any changes in the characteristics of the virus that may threaten human or animal health are detected early. Several OIE Members have reported occurrences of the pandemic H1N1 virus in animals to the OIE as an emerging disease; its occurrence has been reported in pigs in several countries and on one occasion in turkeys. The limited number of documented animal infections have been associated with mild disease and infection of pigs with pandemic H1N1 virus is not considered to be a risk to food safety. OFFLU--the joint OIE-FAO network of expertise on animal influenza--is facilitating exchange of up-to-date technical information about diagnostics, surveillance and the characteristics of the pandemic H1N1 influenza virus in animals. OFFLU is also responsible for collaborating with the human health sector on animal influenza matters that are relevant to public health.

When the influenza pandemic A/H1N1 emerged in 2009, European countries activated their national pandemic plan that were initiated in 2005 when ECDC was established in Stockholm. This agency from the European Commission played its role to strengthen capacities of Member States. ECDC essentially focused attention on surveillance and its reinforcement, epidemic intelligence and guidance. Nevertheless, main challenges remain to be met: continuous adjustment of assumptions, weaknesses in national plans (e.g. no stockpile of antibiotics), paucity of investment in scientific research, no control of transmission from human to animal, persistence of the impact of the pandemic in the subsequent years and eventually the worrying unpreparedness of developing countries that paid a huge toll during previous pandemics.

Naturally occurring regulatory T-cells (Tregs) play a critical role in the homeostasis of healthy immune system. A Treg deficiency is responsible for immune system dysregulation, immune hyperreactivity and autoimmunity. Herein, we investigated the role of Tregs, either in the context of antibody-induced transplantation tolerance, mixed donor/recipient chimerism or in models of spontaneous graft acceptance without immunosuppression. We also investigated their capacities to control endotoxin-mediated immune response in the context of lymphopaenia-driven homeostatic T-cell proliferation. Finally, although Tregs adequately control Th1 and Th2 immunity, they are inefficient in regulating IL-17 producing T cells in vitro and in vivo and rather promote them.

We have proposed that experimental lung fibrosis induced by silica particles is driven by immunosuppression in mice. We showed that the powerful anti-inflammatory cytokine interleukine-10 (IL-10) participates in the development of lung fibrosis by enhancing the expression of pro-fibrotic factors such TGF-beta, IL-4 and IL-13 and by reducing the production anti-fibrotic mediators such as prostaglandin E2. We also reported that Foxp3+ regulatory T cells, known to prevent the development of deleterious inflammatory reactions, are markedly accumulated in the lung and the thymus during the development of silica-induced lung fibrosis in mice. This population controls the intensity of particle-induced inflammatory response and also plays an important direct role in the fibrotic disease. Our findings suggest that in some experimental conditions and patients, immunosuppression instead of inflammation drives fibrotic disease. The mechanism governing immunosuppressive responses should lead to new therapeutic strategies and new diagnostic techniques of lung fibrosis.

During the last twenty years, molecular and biochemical data concerning G-protein coupled receptors have accumulated, providing a detailed characterisation of the structure and functions of this large family of receptors. Initially viewed as simple transducing proteins interacting with intracellular adapters which confer signalling specificity and amplification, the last decade has revealed the extreme complexity and flexibility offered by these membrane receptors. Indeed, there is accumulating evidence that these receptors can interact with several unrelated G-proteins and that some ligands can specifically orientate the functional response. This article summarizes my contributions to the study of the multiplicity and regulation of cell signallings associated with three unrelated systems: the neurotensin receptor, the type 1 metabotropic glutamate receptor and the type 1 cannabinoid receptor. Along with other studies, these experimental data emphasise on the importance of the emerging concept of functional selectivity which should lead to the development of drugs showing enhanced clinical efficacy with lower unwanted side effects.

Cellular metabolism of the amyloid precursor protein (APP) has been widely studied, but the function of the protein remains elusive. APP knock out mice do not show any phenotype, due to in vivo compensation by APLP genes, encoding proteins similar to APP. In order to study the neuronal metabolism of APP, human APP has been expressed in rat cortical neurons in culture. Following differentiation in culture, rat cortical neurons are organized into networks of connected cells, which show neuronal activity in the form of spontaneous and synchronous calcium oscillations. Expression of human APP in these neuronal networks inhibits calcium oscillations, while downregulation of endogenous APP expression increases the frequency and decreases the amplitude of oscillations. Therefore, APP controls neuronal calcium homeostasis and excitability. In the same experimental model, APP is also able to control the neuronal synthesis of cholesterol. Finally, the APP carboxy terminal domain is involved in the epigenetic control of gene expression. Modulation of neuronal expression of APP allows to identify several important functions of the precursor of the amyloid peptide found in senile plaques of Alzheimer disease.

Resistance to infection with enteric pathogens such as Salmonella and Campylobacter can be at many levels and include both non-immune and immune mechanisms. Immune resistance mechanisms can be specific, at the level of the adaptive immune response, or non-specific, at the level of the innate immune response. Whilst we can extrapolate to some degree in birds from what is known about immune responses to these pathogens in mammals, chickens are not "feathered mice", but have a different repertoire of genes, molecules, cells and organs involved in their immune response compared to mammals. Fundamental work on the chicken's immune response to enteric pathogens is therefore still required. Our studies focus particularly on the innate immune response, as responses of heterophils (the avian neutrophil equivalent) from commercial birds, and macrophages from inbred lines of chickens, correlate with resistance or susceptibility to Salmonella infection with a variety of Salmonella serovars and infection models. We work on two basic resistance mechanisms - resistance to colonization with Salmonella or Campylobacter, and resistance to systemic salmonellosis (or fowl typhoid). To map genes involved in resistance to colonization with Salmonella and Campylobacter, we are using a combination of expression quantitative trait loci (eQTLs) from microarray studies, allied with whole genome SNP arrays (WGA), a candidate gene approach and analysis of copy number variation across the genome. For resistance to systemic salmonellosis, we have refined the location ofa novel resistance locus on Chromosome 5, designated SAL1, using high density SNP panels, combined with advanced back-crossing of resistant and susceptible lines. Using a 6th generation backcross mapping population we have confirmed and refined the SAL1 locus to 8-00 kb of Chromosome 5. This region spans 14 genes, including two very striking functional candidates; CD27-binding protein (Siva) and the RAC-alpha serine/threonine protein kinase homologue, AKT1.