Listeriosis cerebral en el modelo murinopatogénesis y prevención

Résumé

Microglia, the innate immune cells of the brain, plays a central role in cerebral listeriosis. In ths work, we present evidence that microglia control Listeria infection differently than macrophages. Infection of primary microglial cultures and murine cell lines with Listeria resulted in a dual function of the two gene expression programmes involved in immune responses in macrophages. Whereas the bacterial gene hly seems responsible for both transcriptional programmes in macrophages, Listeria induces in microglia only the tumor necrosis factor (TNF)-regulated transcriptional programme. Listeria also represses in microglia the late immune response gathered in two clusters, microbial degradation, and interferon (IFN)-inducible genes. The bacterial gene actA was required in microglia to induce TNF-regulated responses and to repress the late response. Isolation of microglial phagosomes revealed a phagosomal environment unable to destroy Listeria. This transcriptional strategy in microglia induced high levels of TNF-α and MCP-1 and low production of other neurotoxic compounds such as nitric oxide, hydrogen peroxide, and Type I IFNs. It´s display a low potential to trigger neuronal apoptosis. This overall bacterial strategy strongly suggests that microglia limit Listeria inflammation pattern through TNF-mediated responses to preserve brain integrity. Clinical cases of neonatal listeriosis are associated with brain morbidities and the loss of fetuses due to complications in early or late pregnancy, arguing microglia function might result altered. We link microglia apoptosis with neonatal listeriosis and listeriosis-associated