Bovine neutrophil chemotaxis to Listeria monocytogenes in neurolisteriosis depends on microglia-released rather than bacterial factors

Abstract

AbstractBackgroundListeria monocytogenes(Lm) 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 againstLm, but on the other hand intracerebral infiltration with PMN is associated with significant neural tissue damage.Lm-PMN interactions in neurolisteriosis are poorly investigated, and factors inducing PMN chemotaxis to infectious foci containingLmin the central nervous system (CNS) remain unidentified.MethodsIn this study, we assessed bovine PMN chemotaxis towardsLmand supernatants of infected endogenous brain cell populations in ex vivo chemotaxis assays, to identify chemotactic stimuli for PMN chemotaxis towardsLmin the brain. In addition, microglial secretion of IL-8 was assessed both ex vivo and in situ.ResultsOur data show that neitherLmcell 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 fromLminfected microglia readily induced chemotaxis of bovine PMN. Microglial expression and secretion of IL-8 was identified during earlyLminfection in vitro and in situ, although IL-8 blocking with a specific antibody could not abrogate PMN chemotaxis towardsLminfected microglial supernatant.ConclusionsThese 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.