No abstract

Antibiotic exposure in children has been associated with the risk of Inflammatory Bowel Disease (IBD). Since antibiotic use in children or in their pregnant mother can affect how the intestinal microbiome develops, we asked whether the transfer of an antibiotic-perturbed microbiota from mothers to their children could affect their risk of developing IBD. Here we demonstrate that germ-free adult pregnant mice inoculated with a gut microbial community shaped by antibiotic exposure transmitted their perturbed microbiota to their offspring with high fidelity. Without any direct or continued exposure to antibiotics, this dysbiotic microbiota in the offspring remained distinct from controls for at least 21 weeks. By using both IL-10-deficient and wild type mothers, we showed that both inoculum and genotype shape the microbiota populations in the offspring. Since IL10−/− mice are genetically susceptible to colitis, we could assess the risk due to maternal transmission of an antibiotic-perturbed microbiota. We found that the IL10−/− offspring that had received the perturbed gut microbiota developed markedly increased colitis. Taken together, our findings indicate that antibiotic exposure shaping the maternal gut microbiota has effects that extend to their offspring with both ecological and long-term disease consequences.

To achieve an adequate response, cells of the immune system must be tightly regulated to avoid hypo-or hyper-responsiveness. One of the mechanisms used by the immune system to avoid excessive inflammation is the modulation of the response through inhibitory receptors containing immunoreceptor tyrosine based inhibitory motifs (ITIM). Here, we show that human neutrophils from peripheral blood express the ITIM containing CD300a (also known as IRp60 and CMRF-35H) receptor. By using the HL-60 differentiation model, we show that the expression of CD300a receptor is developmentally regulated. Stimulation of human neutrophils with LPS and GM-CSF increased the cell surface expression of CD300a as a result of the rapid translocation of an intracellular pool of the receptor to the cell surface. Co-ligation of CD300a with the immunoreceptor tyrosine based activating motif (ITAM) containing CD32a (FcγRIIa) activation receptor inhibited CD32a mediated signaling, whereas it did not inhibit Toll like receptor (TLR)-4 mediated reactive oxygen species (ROS) production. Therefore, at least for human neutrophils, the inhibitory signals mediated by the CD300a receptor may be selective in their action.