Two C57BL/6 mice colonies maintained in two rooms of the same specific pathogen-free (SPF) facility were found to have different gut microbiota and a mucus phenotype that was specific for each colony. The thickness and growth of the colon mucus were similar in the two colonies. However, one colony had mucus that was impenetrable to bacteria or beads the size of bacteria—which is comparable to what we observed in free-living wild mice—whereas the other colony had an inner mucus layer penetrable to bacteria and beads. The different properties of the mucus depended on the microbiota, as they were transmissible by transfer of caecal microbiota to germ-free mice. Mice with an impenetrable mucus layer had increased amounts of Erysipelotrichi, whereas mice with a penetrable mucus layer had higher levels of Proteobacteria and TM7 bacteria in the distal colon mucus. Thus, our study shows that bacteria and their community structure affect mucus barrier properties in ways that can have implications for health and disease. It also highlights that genetically identical animals housed in the same facility can have rather distinct microbiotas and barrier structures.

Secretory immunoglobulin A (SIgA) shields the gut epithelium from luminal antigens and contributes to host-microbe symbiosis. However, how antibody responses are regulated to achieve sustained host-microbe interactions is unknown. We found that mice and humans exhibited longitudinal persistence of clonally related B cells in the IgA repertoire despite major changes in the microbiota during antibiotic treatment or infection. Memory B cells recirculated between inductive compartments and were clonally related to plasma cells in gut and mammary glands. Our findings suggest that continuous diversification of memory B cells constitutes a central process for establishing symbiotic host-microbe interactions and offer an explanation of how maternal antibodies are optimized throughout life to protect the newborn.

Natural killer (NK) cells have not previously been precisely identified or characterized in cattle or any other ruminant species. We have generated a monoclonal antibody against bovine NKp46, which is expressed exclusively by NK cells in man. NKp46 + cells comprised 1-10% of blood mononuclear cells in cattle, and did not stain with antibodies against CD3, CD4, TCR1, B cell or granulocyte markers. The majority of the NKp46 + cells expressed CD2, and a variable fraction also expressed CD8. The tissue distribution of NKp46 + cells in cattle was compatible with the tissue distribution of NK cells in other species. Bovine NKp46 + cells had typical, large granular lymphocyte morphology, and proliferated vigorously in response to bovine IL-2 for a limited number of cell divisions. IL-2-activated NKp46 + cells killed the bovine kidney cell line MDBK. This cytotoxicity was inhibited by preincubation with antibody against NKp46. In a redirected lysis assay, IL-2-activated NKp46 + cells killed the Fc + R + target cell line P815 after preincubation with antibody against NKp46. Together, these data indicate that bovine NKp46 is an activating receptor and demonstrate the existence of a subset of leukocytes in cattle that, in terms of surface markers, morphology and function, represent NK cells.

The gut immune system protects against mucosal pathogens, maintains a mutualistic relationship with the microbiota, and establishes tolerance against food antigens. This requires a balance between immune effector responses and induction of tolerance. Disturbances of this strictly regulated balance can lead to infections or the development inflammatory diseases and allergies. Production of secretory IgA is a unique effector function at mucosal surfaces, and basal mechanisms regulating IgA production have been the focus of much recent research. These investigations have aimed at understanding how long-term IgA-mediated mucosal immunity can best be achieved by oral or sublingual vaccination, or at analyzing the relationship between IgA production, the composition of the gut microbiota, and protection from allergies and autoimmunity. This research has lead to a better understanding of the IgA system; but at the same time seemingly conflicting data have been generated. Here, we discuss how gut IgA production is controlled, with special focus on how differences between T cell-dependent and T cell-independent IgA production may explain some of these discrepancies.

Most of us have experienced deterioration of mood while ill. In humans, immune activation is associated with lethargy and social withdrawal, irritability and aggression; changes in social motivation could, in theory, lead to less functional interactions. This might also be the case for animals housed in close confinement. Tail biting in pigs is an example of damaging social behavior, and sickness is thought to be a risk factor for tail biting outbreaks. One possible mechanism whereby sickness may influence behavior is through cytokines. To identify possible mediators between immune activation and behavioral change, we injected 16 gilts with lipopolysaccharide (LPS; O111:B4; 1.5 μg kg IV through a permanent catheter). In LPS-treated pigs, a significant increase in cortisol, TNF-α, IL-1 receptor antagonist, IL-6, and IL-8 was observed alongside decreased activity within the first 6 h after the injection. CRP was elevated at 12 and 24 h after injection, and food intake was reduced for the first 24 h after injection. Three days post-injection, LPS pigs had lower levels of noradrenaline in their hypothalamus, hippocampus and frontal cortex compared to saline-injected pigs. Pigs injected with LPS also had higher levels of the pro-inflammatory cytokine IFN-γ in their frontal cortex compared to saline-injected pigs. Thus, a low dose of LPS can induce changes in brain cytokine levels and neurotransmitter levels that persist after inflammatory and stress markers in the periphery have returned to baseline levels.