Bénédicte Machiels and Mickaël Dourcy, under the direction of Laurent Gillet (Laboratory of Immunology-Vaccinology (FARAH)), and their colleagues from ULiège and UGent, investigated the imprinting left by the herpesviruses, and more specifically gammaherpesviruses, on the immune system of their host. In fact, gammaherpesviruses (including the Epstein-Barr virus, responsible for infectious mononucleosis in humans) are very common viruses having co-evolved with their host to establish persistent infections. While these gammaherpesviruses favour regulatory immune responses to maintain their latent state, researchers are interested in the existence of a symbiotic relationship between these agents and their host.
In their study published in Nature Immunology, the researchers showed that infecting mice in a laboratory with a gammaherpesvirus, Murid Herpesvirus 4 (MuHV-4), protects the latter from developing allergic asthma. Interestingly, the results obtained revealed that a respiratory infection with MuHV-4 caused the death of alveolar macrophages and the concomitant recruitment of innate immune cells among with monocytes at the inflammation site. These monocytes, originating from bone marrow, were able to reconstitute the alveolar niche and differentiate into mature macrophages in the long term. In addition, unlike alveolar macrophages from non-infected individuals, these recruited monocytes presented regulatory properties responsible for the inhibition of the allergic pulmonary response.
These results shine a new light on the origin of populations of macrophages in an infectious context and prove, for the first time, that a viral infection can induce the replacement of a population of resident embryonic macrophages with regulatory monocytes.
In addition, this study highlights the determining effect of antigenic infections or stimulations from a young age for the subsequent development of immune responses, confirming the hygiene hypothesis, according to which the increase in allergies in our countries is a result of the reduction in infections during childhood. Therefore, this study is the first to reveal the crucial role that some viral infections can play in the long-term control of the development of allergic responses. At a time when the incidence of these immunopathologies continues to increase, understanding of the molecular mechanisms at the origin of the regulatory properties induced by gammaherpesviruses could see the emergence of new medical perspectives.