Early-life vitamin A treatment rescues neonatal infection-induced durably impaired tolerogenic properties of celiac lymph nodes.

Gut-draining mesenteric and celiac lymph nodes (mLNs and celLNs) critically contribute to peripheral tolerance toward food and microbial antigens by supporting the de novo induction of regulatory T cells (Tregs). These tolerogenic properties of mLNs and celLNs are stably imprinted within stromal cells (SCs) by microbial signals and vitamin A (VA), respectively. Here, we report that a single, transient gastrointestinal infection in the neonatal, but not adult, period durably abrogates the efficient Treg-inducing capacity of celLNs by altering the subset composition and gene expression profile of celLNSCs. These cells carry information about the early-life pathogen encounter until adulthood and durably instruct migratory dendritic cells entering the celLN with reduced tolerogenic properties. Mechanistically, transiently reduced VA levels cause long-lasting celLN functional impairment, which can be rescued by early-life treatment with VA. Together, our data highlight the therapeutic potential of VA to prevent sequelae post gastrointestinal infections in infants.

Distinct Polysaccharide Utilization Determines Interspecies Competition between Intestinal Prevotella spp.

Prevotella spp. are a dominant bacterial genus within the human gut. Multiple Prevotella spp. co-exist in some individuals, particularly those consuming plant-based diets. Additionally, Prevotella spp. exhibit variability in the utilization of diverse complex carbohydrates. To investigate the relationship between Prevotella competition and diet, we isolated Prevotella species from the mouse gut, analyzed their genomes and transcriptomes in vivo, and performed competition experiments between species in mice. Diverse dominant Prevotella species compete for similar metabolic niches in vivo, which is linked to the upregulation of specific polysaccharide utilization loci (PULs). Complex plant-derived polysaccharides are required for Prevotella spp. expansion, with arabinoxylans having a prominent impact on species abundance. The most dominant Prevotella species encodes a specific tandem-repeat trsusC/D PUL that enables arabinoxylan utilization and is conserved in human Prevotella copri strains, particularly among those consuming a vegan diet. These findings suggest that efficient (arabino)xylan-utilization is a factor contributing to Prevotella dominance.

Comparative analysis of the expression patterns of eight suppressors of cytokine signaling in tongue sole, Cynoglossus semilaevis.

Suppressor of cytokine signaling (SOCS) family members are inhibitors of cytokine signaling pathways and key regulators of immunological homeostasis. They have been extensively studied in mammalian models, but systematic analyses of SOCS in fish are limited. In the current study, a total of eight SOCS genes from tongue sole (Cynoglossus semilaevis) were characterized. All eight CsSOCS exhibit conserved structures of SOCS and were phylogenetically grouped together with the respective SCOS members known in mammalian and teleost species. Under normal physiological conditions, the expressions of the eight CsSOCS genes were detected at varied levels in nine major tissues, with most CsSOCS highly expressed in kidney. Following challenge with intracellular and extracellular bacterial pathogens, the majority of CsSOCS genes exhibited distinctly different expression profiles in a time-, tissue-, and pathogen-dependent manner. In general, intracellular pathogen caused wider and higher levels of CsSOCS expressions than extracellular pathogen. These results suggest that different members of SOCSs in teleost may play different roles in the infection processes of different bacterial pathogens.

Molecular characterization and expression analysis of nine CC chemokines in half-smooth tongue sole, Cynoglossus semilaevis.

Chemokines are a large, diverse group of small cytokines that can be classified into several families, including the CC chemokine family, which plays a pivotal role in host defense by inducing leukocyte chemotaxis under physiological and inflammatory conditions. Here we studied 9 CC chemokines from half-smooth tongue sole (Cynoglossus semilaevis). Phylogenetic analysis divided these chemokines into four groups. The tissue specific expression patterns of the 9 chemokines under normal physiological conditions varied much, with most chemokines highly expressed in immune organs, while some other chemokines showing high expression levels in non-immune organs. In addition, the 9 chemokines exhibited similar or distinctly different expression profiles in response to the challenge of virus and intracellular and extracellular bacterial pathogens. These results indicate that in tongue sole, CC chemokines may be involved in different immune responses as homeostatic or inflammatory chemokines.