RESUMO
In recent decades, bats have been associated with numerous viral pandemics. Bats harbor a large variety of viruses, some of which have a high zoonotic potential for humans. While infection with these viruses can be fatal in other mammals, bats are often infected asymptomatically. It is hypothesized that a balanced immune response would enable them to maintain homeostasis during infection, thus limiting viral replication while avoiding the impact of excessive inflammation. Deciphering these mechanisms, using adapted in vitro models, will help assess and avoid the potential zoonotic risk of these animals, while paving the way for the development of therapeutics for infectious and inflammatory diseases.
Title: Des chauves-souris et des virus - Entre contrôle de l'infection et tolérance immunitaire. Abstract: Durant les dernières décennies, les chauves-souris ont été associées à de nombreuses pandémies virales. Ces animaux hébergent en effet une diversité importante de virus, certains à potentiel zoonotique pour l'homme. Alors que ces virus peuvent être mortels chez d'autres mammifères, les chauves-souris sont souvent infectées de façon asymptomatique. La mise en place d'une réponse immunitaire équilibrée leur permettrait de maintenir l'homéostasie lors de l'infection, en limitant la réplication virale tout en évitant l'impact d'une inflammation trop importante. Le décryptage de ces mécanismes, à l'aide de modèles in vitro adaptés, devrait contribuer à évaluer et à éviter le risque zoonotique potentiel de ces animaux, tout en ouvrant la voie au développement de thérapeutiques pour les maladies infectieuses et inflammatoires.
Assuntos
Quirópteros , Vírus , Animais , Humanos , Tolerância Imunológica , Homeostase , Controle de InfecçõesRESUMO
BACKGROUND: Coevolution between pathogens and their hosts decreases host morbidity and mortality. Bats host and can tolerate viruses which can be lethal to other vertebrate orders, including humans. Bat adaptations to infection include localized immune response, early pathogen sensing, high interferon expression without pathogen stimulation, and regulated inflammatory response. The immune reaction is costly, and bats suppress high-cost metabolism during torpor. In the temperate zone, bats hibernate in winter, utilizing a specific behavioural adaptation to survive detrimental environmental conditions and lack of energy resources. Hibernation torpor involves major physiological changes that pose an additional challenge to bat-pathogen coexistence. Here, we compared bat cellular reaction to viral challenge under conditions simulating hibernation, evaluating the changes between torpor and euthermia. RESULTS: We infected the olfactory nerve-derived cell culture of Myotis myotis with an endemic bat pathogen, European bat lyssavirus 1 (EBLV-1). After infection, the bat cells were cultivated at two different temperatures, 37 °C and 5 °C, to examine the cell response during conditions simulating euthermia and torpor, respectively. The mRNA isolated from the cells was sequenced and analysed for differential gene expression attributable to the temperature and/or infection treatment. In conditions simulating euthermia, infected bat cells produce an excess signalling by multitude of pathways involved in apoptosis and immune regulation influencing proliferation of regulatory cell types which can, in synergy with other produced cytokines, contribute to viral tolerance. We found no up- or down-regulated genes expressed in infected cells cultivated at conditions simulating torpor compared to non-infected cells cultivated under the same conditions. When studying the reaction of uninfected cells to the temperature treatment, bat cells show an increased production of heat shock proteins (HSPs) with chaperone activity, improving the bat's ability to repair molecular structures damaged due to the stress related to the temperature change. CONCLUSIONS: The lack of bat cell reaction to infection in conditions simulating hibernation may contribute to the virus tolerance or persistence in bats. Together with the cell damage repair mechanisms induced in response to hibernation, the immune regulation may promote bats' ability to act as reservoirs of zoonotic viruses such as lyssaviruses.
