The bacterium Listeria monocytogenes ( Lm) is widely distributed in the environment as a saprophyte, but may turn into a lethal intracellular pathogen upon ingestion. Invasive infections occur in numerous species worldwide, but most commonly in humans and farmed ruminants, and manifest as distinct forms. Of those, neuroinfection is remarkably threatening due to its high mortality. Lm is widely studied not only as a pathogen but also as an essential model for intracellular infections and host-pathogen interactions. Many aspects of its ecology and pathogenesis, however, remain unclear and are rarely addressed in its natural hosts. This review highlights the heterogeneity and adaptability of Lm by summarizing its association with the environment, farm animals, and disease. It also provides current knowledge on key features of the pathology and (molecular) pathogenesis of various listeriosis forms in naturally susceptible species with a special focus on ruminants and on the neuroinvasive form of the disease. Moreover, knowledge gaps on pathomechanisms of listerial infections and relevant unexplored topics in Lm pathogenesis research are highlighted.

Evidence is growing that microglia adopt different roles than monocyte‐derived macrophages (MDM) during CNS injury. However, knowledge about their function in the pathogenesis of neuroinfections is only rudimentary. Cattle are frequently affected by neuroinfections that are either zoonotic or related to diseases in humans, and, hence, studies of bovine neuroinfections as a natural disease model may generate fundamental data on their pathogenesis potentially translatable to humans. We investigated the transcriptomic landscape and lineage markers of bovine microglia and MDM. Although bovine microglia expressed most microglial signature genes known from humans and mice, they exhibited a species‐specific transcriptomic profile, including strikingly low expression of TMEM119 and enrichment of the two scavenger receptors MEGF10 and LY75. P2RY12 was amongst the most enriched genes in bovine microglia, and antibodies against P2RY12 labeled specifically resting microglia, but also reactive microglia within neuroinfection foci in‐situ. On the other hand, F13A1 was amongst the most enriched genes in bovine monocytes and MDM and, additionally, the encoded protein was expressed in‐situ in monocytes and MDM in the inflamed brain but not in microglia, making it a promising marker for infiltrating MDM in the brain. In culture, primary bovine microglia downregulated signature genes, expressed markers of activation, and converged their transcriptome to MDM. However, they retained several microglia signature genes that clearly distinguished them from bovine MDM, making them a promising in‐vitro tool to study mechanisms of microglia–pathogen interactions.

The availability of endogenous and dietary carbohydrates in the gastrointestinal tract influences the composition of the gut microbiota. Carbohydrate foraging requires the action of bacterially-encoded glycoside hydrolases, which release mono- and oligosaccharides taken up as carbon sources by multiple microbial taxa. In addition to providing nutrients to the microbiota, the cleavage of host glycans by bacterial glycoside hydrolases may alter the properties of surface glycoproteins involved in cell adhesion and activation processes in the gut lumen. To investigate the impact of bacterial glycoside hydrolase activities on the gut microbial composition and on host glycans during colon inflammation, we increased local glycoside hydrolase activity by supplementing mice with recombinant E. coli expressing specific sialidase, fucosidase and rhamnosidase enzymes during acute colitis induced by dextran sulfate sodium ingestion. Whereas increased fucosidase and rhamnosidase activity did not alter the course of colitis, increased sialidase activity exacerbated disease severity. The effect of increased sialidase activity on inflammation was not caused by changes in the microbial composition given that a similar shift in gut bacteria occurred in all groups of mice supplemented with recombinant E. coli. Increased sialidase activity in the colon of treated mice however significantly altered the distribution of sialic acid on mucosal glycans. Treatment of lamina propria dendritic cells with bacterial sialidase also strongly decreased the density of sialylated ligands to anti-inflammatory siglec lectins, indicating that the remodeling of surface sialylation caused by increased sialidase activity likely accounts for the observed exacerbation of acute colitis in mice.