PTH induces bone loss via microbial-dependent expansion of intestinal TNF+ T cells and Th17 cells.

Bone loss is a frequent but not universal complication of hyperparathyroidism. Using antibiotic-treated or germ-free mice, we show that parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched by the Th17 cell-inducing taxa segmented filamentous bacteria (SFB). SFB+ microbiota enabled PTH to expand intestinal TNF+ T and Th17 cells and increase their S1P-receptor-1 mediated egress from the intestine and recruitment to the bone marrow (BM) that causes bone loss. CXCR3-mediated TNF+ T cell homing to the BM upregulated the Th17 chemoattractant CCL20, which recruited Th17 cells to the BM. This study reveals mechanisms for microbiota-mediated gut-bone crosstalk in mice models of hyperparathyroidism that may help predict its clinical course. Targeting the gut microbiota or T cell migration may represent therapeutic strategies for hyperparathyroidism.

[Research into the immunogenic properties of the recombinant cellulose-binding domain of Anaerocellum thermophilum in vivo].

Development of new technology allows different antigens of a necessary degree of cleanliness to be obtained. This development is a major problem of modern medical biotechnology. A promising approach to this problem includes use of the affinity domains (tags) incorporated in structure of a recombinant antigen and capable to bind to corresponding sorbents. The method of preparation of ready-for-use injections containing complexes formed by soluble antigens on insoluble cellulose immunosorbent (not chemical conjugates) in one stage is based on the fusion protein technology. This approach includes preparation of two-component recombinant proteins containing an antigen of interest and the cellulose-binding domain (CBD), which spontaneously binds to cellulose containing sorbents with high binding constant. Research into the immunogenic properties of the CBD in the complex with cellulose and in the preparation of recombinant CBD in a rat model was performed. The titers of specific antibodies in rat serum induced by recombinant CBD and CBD in the complex with cellulose was evaluated. The CBD in the complex with cellulose was more immunogenic in comparison with CBD alone. The spectrum and levels of cytokines in collected rat serum induced by developed preparations was also measured using the microsphere-based Luminex Flowmetrix system (BioPlex). It was found that the amorphous cellulose was not an immunotolerant sorbent, because it induced the expression of the proinfammatory cytokines in vivo.

Bacterial probiotics induce an immune response in the honey bee (Hymenoptera: Apidae).

To explore immune system activation in the honey bee, Apis mellifera L., larvae of four ages were exposed through feeding to spores of a natural pathogen, Paenibacillus larvae larvae, to cells of a diverse set of related nonpathogenic bacteria, and to bacterial coat components. These larvae were then assayed for RNA levels of genes encoding two antibacterial peptides, abaecin and defensin. Larvae exposed to either P. l. larvae or a mix of nonpathogenic bacteria showed high RNA levels for the abaecin gene relative to controls. First instars responded significantly to the presence of the nonpathogenic mix within 12 h after exposure, a time when they remain highly susceptible to bacterial invasion. This response was sustained for two successive instars, eventually becoming 21-fold higher in larvae exposed to probiotic spores versus control larvae. The mixture of nonpathogenic bacteria is therefore presented as a potential surrogate for assaying the immune responses of different honey bee lineages. It also is proposed that nonpathogenic bacteria can be used as a probiotic to enhance honey bee immunity, helping bee larvae, and other life stages, survive attacks from pathogens in the field.