The conserved immune response in both mouse and human to these previously unknown flagellins of the microbiota indicate that they play an important role in host-microbe interactions in the intestine.

Background While immune responses directed against antigens from the intestinal microbiota are observed in certain diseases, the normal human adaptive immune response to intestinal microbiota is poorly defined. Objective Our goal was to assess the adaptive immune response to the intestinal microbiota present in 143 healthy adults and compare this response to the immune response observed in 52 children and their mothers at risk of having allergic disease. Methods Human serum was collected from adults and from children followed from birth to seven years of age, and the serum IgG response to a panel of intestinal microbiota antigens was assessed using a novel protein microarray. Results Nearly every individual tested, regardless of health status, had serum IgG that recognized a common set of antigens. Seroreactivity to the panel of antigens was significantly lower in atopic adults. Healthy infants expressed the highest level of IgG seroreactivity to intestinal microbiota antigens. This adaptive response developed between 6 and 12 months of age, and peaked around 2 years of age. Low IgG responses to certain clusters of microbiota antigens during infancy were associated with allergy development during childhood. Conclusions There is an observed perturbation of the adaptive response to antigens from the microbiota in allergic individuals. These perturbations are observable even in childhood, suggesting that optimal stimulation of the adaptive immune system by the microbiota may be needed to prevent certain immune-mediated diseases.

Porphyromonas (Bacteroides) gingivalis W12 binds and degrades human plasma fibronectin. In the presence of the protease inhibitor N-a-p-tosyl-L-lysyl chloromethyl ketone, P. gingivalis cells accumulated substantial amounts of '2,I-fibronectin as a function of incubation time. Fibronectin binding was specific, reversible, and

The cellular and molecular mechanisms of gonadotrope desensitization are unknown but transduction of the GnRH signal is known to involve sequentially the GnRH receptor, Gq alpha protein, phospholipase C beta-1, inositol-1,4,5-trisphosphate (IP3), and intracellular Ca+2 release. Here, we report the results of studies of a new family of proteins known as regulators of G protein signaling (RGS) that recently have been implicated in desensitization of several ligand induced processes. Using DNA-mediated transfection, we co-expressed the GnRH receptor and RGS1,2,3, or 4 in COS-1 cells. Control cells and those expressing RGS1,2, and 4 produced five fold increases in IP3 levels during the 30 sec after treatment with GnRH. In contrast, RGS3 expression suppressed by 75% the GnRH-induced IP3 responses. RGS3 was shown to bind Gq alpha protein in a model in vitro system: recombinant RGS3-glutathione-S-transferase (GST) fusion protein bound five-fold more 35S-met labeled Gq alpha protein than did with GST alone, suggesting that the mechanism of RGS3 action is attenuation of Gq alpha protein activation of phospholipase C. RGS3 mRNA and protein were observed to be expressed endogenously in the gonadotropic alpha T3-1 cell line. These results suggest a potential role for RGS3 in modulating the LH secretory responsiveness of the pituitary gonadotrope to GnRH.

Summary Commensal flora plays an important role in the development of the mucosal immune system and in maintaining intestinal homeostasis. However, the mechanisms involved in regulation of host-microbiota interaction are still not completely understood. In this study, we examined how microbiota and intestinal inflammatory conditions regulate host microRNA expression and observed lower microRNA-107 (miR-107) expression in the inflamed intestines of colitic mice, compared with that in normal control mice. miR-107 was predominantly reduced in epithelial cells and CD11c+ myeloid cells including dendritic cells and macrophages in the inflamed intestines. We demonstrate that IL-6, IFN-γ and TNF-α downregulated, whereas TGF-β promoted, miR-107 expression. In addition, miR-107 expression was higher in the intestines of germ-free mice than in mice housed under specific pathogen-free conditions, and the presence of microbiota downregulated miR-107 expression in DCs and macrophages in a MyD88- and NF-κB-dependent manner. We determined that the ectopic expression of miR-107 specifically repressed the expression of IL-23p19, a key molecule in innate immune responses to commensal bacteria. We concluded that regulation of miR-107 by intestinal microbiota and pro-inflammatory cytokine serve as an important pathway for maintaining intestinal homeostasis.