Uropathogenic Escherichia coli (UPEC) are a common cause of urinary tract infections (UTIs) in humans. While the importance of natural killer (NK) cells in innate immune protection against tumors and viral infections is well documented, their role in defense against bacterial infections is still emerging, and their involvement in UPEC-mediated UTI is practically unknown. Using a systematic mutagenesis approach, we found that UPEC adheres to NK cells primarily via its type I fimbriae and employs its hemolysinA toxin to kill NK cells. In the absence of hemolysinA, NK cells directly respond to the bacteria and secrete the cytokine TNF-α, which results in decreased bacterial numbers in vitro and reduction of bacterial burden in the infected bladders. Thus, NK cells control UPEC via TNF-α production, which UPEC counteracts by hemolysinA-mediated killing of NK cells, representing a previously unrecognized host defense and microbial counterattack mechanism in the context of UTI.

Orthodontic tooth movement (OTM) is a “sterile” inflammatory process. The present study aimed to reveal the underlying biological mechanisms, by studying the force associated-gene expression changes, in a time-dependent manner. Ni-Ti springs were set to move the upper 1st-molar in C57BL/6 mice. OTM was measured by μCT. Total-RNA was extracted from tissue blocks at 1,3,7 and 14-days post force application, and from two control groups: naïve and inactivated spring. Gene-expression profiles were generated by next-generation-RNA-sequencing. Gene Set Enrichment Analysis, K-means algorithm and Ingenuity pathway analysis were used for data interpretation. Genes of interest were validated with qRT-PCR. A total of 3075 differentially expressed genes (DEGs) were identified, with the greatest number at day 3. Two distinct clusters patterns were recognized: those in which DEGs peaked in the first days and declined thereafter (tissue degradation, phagocytosis, leukocyte extravasation, innate and adaptive immune system responses), and those in which DEGs were initially down-regulated and increased at day 14 (cell proliferation and migration, cytoskeletal rearrangement, tissue homeostasis, angiogenesis). The uncovering of novel innate and adaptive immune processes in OTM led us to propose a new term “Immunorthodontics”. This genomic data can serve as a platform for OTM modulation future approaches.

Sustained mechanical forces applied to tissue are known to shape local immunity. In the oral mucosa, mechanical stress, either naturally induced by masticatory forces or externally via mechanical loading during orthodontic tooth movement (OTM), is translated, in part, by T cells to alveolar bone resorption. Nevertheless, despite being considered critical for OTM, depletion of CD4+ and CD8+ T cells is reported to have no impact on tooth movement, thus questioning the function of αβT cells in OTM-associated bone resorption. To further address the role of T cells in OTM, we first characterized the leukocytes residing in the periodontal ligament (PDL), the tissue of interest during OTM, and compared it to the neighboring gingiva. Unlike the gingiva, monocytes and neutrophils represent the major leukocytes of the PDL. These myeloid cells were also the main leukocytes in the PDL of germ-free mice, although at lower levels than SPF mice. T lymphocytes were more enriched in the gingiva than the PDL, yet in both tissues, the relative fraction of the γδT cells was higher than the αβ T cells. We thus sought to examine the role of γδT cells in OTM. γδT cells residing in the PDL were mainly Vγ6+ and produced interleukin (IL)–17A but not interferon-γ. Using Tcrd-GDL mice allowing conditional ablation of γδT cells in vivo, we demonstrate that OTM was greatly diminished in the absence of γδT cells. Further analysis revealed that ablation of γδT cells decreased early IL-17A expression, monocyte and neutrophil recruitment, and the expression of the osteoclastogenic molecule receptor activator of nuclear factor–κβ ligand. This, eventually, resulted in reduced numbers of osteoclasts in the pressure site during OTM. Collectively, our data suggest that γδT cells are essential in OTM for translating orthodontic mechanical forces to bone resorption, required for relocating the tooth in the alveolar bone.

BackgroundThe aim of the study is to examine bone healing following augmentation with allograft or β‐tricalcium phosphate (β‐TCP) and evaluate orthodontic tooth movement (OTM) into the augmented sites.MethodsThe study included two parts. Part I included the alveolar bone regeneration model. Osseous defects were created by extraction of the maxillary first molars in C57BL/6 mice, and the sockets were filled with allograft, β‐TCP, or left unfilled (n = 6/group). Mouse allograft was prepared by a novel method using long bones. Maxillae were collected at 2, 4, and 6 weeks for microcomputed tomography (μCT) and histological analysis. In Part II, OTM was performed after full bone healing, through grafted and unfilled sockets (n = 10/group), and the second molar shift was assessed using μCT.ResultsBone volume and trabeculation were reduced in β‐TCP compared with allograft and non‐grafted groups at 2 and 4 weeks post‐grafting, but similar at 6 weeks. Graft particles could be detected at 2 weeks post‐grafting for β‐TCP, and at 2 and 4 weeks for allograft. Increased osteoclasts’ presence was observed in the β‐TCP group at 2 and 4 weeks compared with allograft and control. OTM was similar in the two graft groups, but impaired versus the non‐grafted controls.Conclusionβ‐TCP and allograft induce full normal healing but alter OTM into the regenerated sites.

The two novel mouse models show that the lack of resorption of BB xenografts renders them inadequate for proper orthodontic tooth movement at a later stage.