Beschreibung:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p><jats:italic>Listeria monocytogenes</jats:italic>(<jats:italic>Lm</jats:italic>) is a bacterial pathogen of major concern for humans and ruminants due to its neuroinvasive potential and its ability to cause deadly encephalitis (neurolisteriosis). On one hand, polymorphonuclear neutrophils (PMN) are key players in the defense against<jats:italic>Lm</jats:italic>, but on the other hand intracerebral infiltration with PMN is associated with significant neural tissue damage.<jats:italic>Lm</jats:italic>-PMN interactions in neurolisteriosis are poorly investigated, and factors inducing PMN chemotaxis to infectious foci containing<jats:italic>Lm</jats:italic>in the central nervous system (CNS) remain unidentified.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this study, we assessed bovine PMN chemotaxis towards<jats:italic>Lm</jats:italic>and supernatants of infected endogenous brain cell populations in ex vivo chemotaxis assays, to identify chemotactic stimuli for PMN chemotaxis towards<jats:italic>Lm</jats:italic>in the brain. In addition, microglial secretion of IL-8 was assessed both ex vivo and in situ.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Our data show that neither<jats:italic>Lm</jats:italic>cell wall components nor intact bacteria elicit chemotaxis of bovine PMN ex vivo. Moreover, astrocytes and neural cells fail to induce bovine PMN chemotaxis upon infection. In contrast, supernatant from<jats:italic>Lm</jats:italic>infected microglia readily induced chemotaxis of bovine PMN. Microglial expression and secretion of IL-8 was identified during early<jats:italic>Lm</jats:italic>infection in vitro and in situ, although IL-8 blocking with a specific antibody could not abrogate PMN chemotaxis towards<jats:italic>Lm</jats:italic>infected microglial supernatant.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>These data provide evidence that host-derived rather than bacterial factors trigger PMN chemotaxis to bacterial foci in the CNS, that microglia have a primary role as initiators of bovine PMN chemotaxis into the brain during neurolisteriosis and that blockade of these factors could be a therapeutic target to limit intrathecal PMN chemotaxis and PMN associated damage in neurolisteriosis.</jats:p></jats:sec>