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Size and composition of γδ T cell populations change dramatically with tissue location, during development, and in disease. Given the functional differentiation of γδ T cell subsets, such shifts might alter the impact of γδ T cells on the immune system. To test this concept, and to determine if γδ T cells can affect other immune cells prior to an immune response, we examined non-immunized mice derived from strains with different genetically induced deficiencies in γδ T cells, for secondary changes in their immune system. We previously saw extensive changes in pre-immune antibodies and B cell populations. Here, we report effects on αβ T cells. Similarly to the B cells, αβ T cells evidently experience the influence of γδ T cells at late stages of their pre-immune differentiation, as single-positive heat stable antigen-low thymocytes. Changes in these and in mature αβ T cells were most prominent with memory-phenotype cells, including both CD8+ and CD4+ populations. As previously observed with B cells, most of the effects on αβ T cells were dependent on IL-4. Unexpectedly, IL-4 seemed to be produced mainly by αβ T cells in the non-immunized mice, albeit strongly regulated by γδ T cells. Similarly to our findings with B cells, changes of αβ T cells were less pronounced in mice lacking all γδ T cells than in mice lacking only some, suggesting that the composition of the γδ T cell population determines the nature of the γδ-influence on the other pre-immune lymphocytes.

Background: The purpose of this 6‐week, single‐blinded, randomized clinical trial was to determine if the use of an interproximal brush, with or without a tracking device, is more effective than an oral irrigator in improving interproximal probing depth (PD), clinical attachment level (CAL), plaque index (PI), gingival index (GI), bleeding on probing (BOP), and inflammatory markers. Methods: Seventy‐six patients with Stages III–IV, Grade B periodontitis and a 5–7 mm posterior interproximal PD with BOP were randomized: (1) interproximal brush alone (IB; n = 26), (2) interproximal brush with tracking device (TD; n = 23), (3) oral irrigator (OI; n = 27). Participants used devices once daily for 6 weeks. Clinical measurements (PD, CAL, PI, BOP, GI) and gingival crevicular fluid (GCF) samples were collected at baseline and 6 weeks. Results: All groups showed a significant reduction in PD and CAL (≥1.1 mm, p < 0.0001) and improvement in BOP (≥56%, p < 0.0001) and GI (≥82%, p < 0.001) at the experimental site with no differences among groups. The IB and IB+TD groups showed a significant reduction in PI (≥0.9, p ≤ 0.01). Interleukin (IL)‐1β was reduced in all groups (p = 0.006), but IB+TB more than OI (p ≤ 0.05). IL‐10 was reduced among all groups (p = 0.01), while interferon‐gamma significantly increased (p = 0.01) in all groups. Conclusions: IB and OI improved clinical parameters of PD and CAL and reduced inflammatory markers (BOP, GI, GCF IL‐1β). IB had better interproximal plaque reduction. Tracking did not significantly improve clinical parameters compared with the IB and OI groups, suggesting future modifications are needed. [ABSTRACT FROM AUTHOR]

Bacteria express many small RNAs for which the regulatory roles in pathogenesis have remained poorly understood due to a paucity of robust phenotypes in standard virulence assays. Here we use a generic 'dual RNA-seq' approach to profile RNA expression simultaneously in pathogen and host during Salmonella enterica serovar Typhimurium infection and reveal the molecular impact of bacterial riboregulators. We identify a PhoP-activated small RNA, PinT, which upon bacterial internalization temporally controls the expression of both invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity causes pervasive changes in coding and noncoding transcripts of the host. Interspecies correlation analysis links PinT to host cell JAK-STAT signalling, and we identify infectionspecific alterations in multiple long noncoding RNAs. Our study provides a paradigm for a sensitive RNA-based analysis of intracellular bacterial pathogens and their hosts without physical separation, as well as a new discovery route for hidden functions of pathogen genes., Regulatory RNAs crucially contribute to post-transcriptional control of gene expression in a wide array of organisms, including pathogenic bacteria (1-3). The facultative intracellular pathogen Salmonella enterica serovar Typhimurium (hereafter referred [...]

Background: The objective of this exploratory study was to evaluate inflammatory markers in periodontal maintenance patients from a randomized, double-masked, parallel intervention clinical trial comparing local simvastatin (SIM) to carrier alone following mini-flap access.Methods: Fifty patients with a 6-9-mm inflamed pocket during periodontal maintenance therapy (PMT) were treated with papilla reflection (PR)/root planing and placement of 2.2-mg simvastatin in methylcellulose (SIM/MCL) or methylcellulose alone (MCL). A small piece of interproximal soft tissue was harvested at baseline and 2 weeks postoperatively, gingival crevicular fluid (GCF) obtained at baseline, 2 weeks and 12 months, and bleeding on probing (BOP) and clinical attachment level (CAL) were measured at baseline and 12 months. Pro-inflammatory interleukin (IL)-6 and anti-inflammatory IL-10 gene activation were determined by reverse transcriptase polymerase chain reaction (rt-PCR). GCF IL-1β, IL-6, IL-10, and vascular endothelial growth factor (VEGF-A) were measured with multiplex technology. Comparisons between groups and over time used logistic regression and general estimating equations. Associations between inflammatory markers and 12-month outcomes used Wilcoxon rank sum tests or Pearson correlations.Results: Patients in the SIM group had 4.17 greater odds (p = 0.047) of improved BOP at 12 months. Median IL-6 and VEGF were significantly increased for all patients after 2 weeks of healing (p < 0.0001 and p = 0.03, respectively), while median IL-10 gene activation was increased after 2 weeks in SIM/MCL (NS). Overall, elevated GCF IL-10 at 2 weeks was significantly correlated with improved CAL at 12 months (r = -0.32, p = 0.03).Conclusions: Local SIM/MCL may have anti-inflammatory effects that potentially are associated with improved long-term CAL outcomes. [ABSTRACT FROM AUTHOR]

RNA helicases play crucial roles in RNA biology. In plants, RNA helicases are encoded by large gene families, performing roles in abiotic stress responses, development, the post-transcriptional regulation of gene expression, as well as housekeeping functions. Several of these RNA helicases are targeted to the organelles, the mitochondria and chloroplasts. Cyanobacteria are the direct evolutionary ancestors of plant chloroplasts. The cyanobacterium Synechocystis 6803 encodes a single DEAD-box RNA helicase, CrhR, that is induced by a range of abiotic stresses, including low temperature. Though the Δ crhR mutant exhibits a severe cold-sensitive phenotype, the physiological function(s) performed by CrhR have not been described. To identify transcripts interacting with CrhR, we performed RNA co-immunoprecipitation with extracts from a Synechocystis crhR deletion mutant expressing the FLAG-tagged native CrhR or a K57A mutated version with an anticipated enhanced RNA binding. The composition of the interactome was strikingly biased towards photosynthesis-associated and redox-controlled transcripts. A transcript highly enriched in all experiments was the crhR mRNA, suggesting an autoregulatory molecular mechanism. The identified interactome explains the described physiological role of CrhR in response to the redox poise of the photosynthetic electron transport chain and characterizes CrhR as an enzyme with a diverse range of transcripts as molecular targets. [ABSTRACT FROM AUTHOR]