Signaling through Toll-like receptors (TLR) activates dendritic cell (DC) maturation and IL-12 production, which directs the induction of Th1 cells. We found that the production of IL-10, in addition to inflammatory cytokines and chemokines, was significantly reduced in DCs from TLR4-defective C3H/HeJ mice in response to Bordetella pertussis. TLR4 was also required for B. pertussis LPS-induced maturation of DCs, but other B. pertussis components stimulated DC maturation independently of TLR4. The course of B. pertussis infection was more severe in C3H/HeJ than in C3H/HeN mice. Surprisingly, Ab- and Ag-specific IFN-γ responses were enhanced at the peak of infection, whereas Ag-specific IL-10-producing T cells were significantly reduced in C3H/HeJ mice. This was associated with enhanced inflammatory cytokine production, cellular infiltration, and severe pathological changes in the lungs of TLR4-defective mice. Our findings suggest that TLR-4 signaling activates innate IL-10 production in response to B. pertussis, which both directly, and by promoting the induction of IL-10-secreting type 1 regulatory T cells, may inhibit Th1 responses and limit inflammatory pathology in the lungs during infection with B. pertussis.

IFN-gamma plays a critical role in protection against Bordetella pertussis, but Th1 cells are only detectable after the infection has started to resolve, suggesting a protective role for innate IFN-gamma early in infection. Here, we demonstrate significant recruitment of NK cells and NKT cells into the lungs following respiratory challenge with B. pertussis. Furthermore, NK cells are the primary source of IFN-gamma in the lungs during the acute stage of infection. Stimulation of IFN-gamma production by NK cells was indirect through B. pertussis-activated IL-12 or IL-23 production by dendritic cells. Depletion of NK cells with anti-asialo ganglio-N-tetraosylceramide antibody resulted in a lethal infection, with enhancement of bacterial load in the lungs and dissemination of the bacteria to the liver via the blood. NK cell-depleted mice had significantly reduced B. pertussis-specific IFN-gamma and enhanced IgG1 and IL-5, but not IL-10 production, suggesting that regulatory T cells are induced simultaneously with Th1 cells, but the absence of NK cells resulted in enhancement of Th2-type responses. These findings suggest that NK cells confer resistance to B. pertussis by activating IL-12-mediated production of IFN-gamma, which enhances the anti-bacterial activity of macrophages, but also promotes the differentiation of Th1 cells.

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Background:  There has been little published about the nature and frequency of suicidal phenomena in children compared to that of adolescents. Method:  Standardised information on all presentations with suicidal phenomena to the Children’s University Hospital, Dublin from 2002 to 2008 were retrospectively analysed from a centralised database. Results:  During the time period of the study, 401 young people presented for assessment, of whom 21.9% (N = 88) were under 12 years of age. Children differed from adolescents in terms of gender distribution, method of self‐harm, and risk factors present. Conclusion:  Children under 12 are capable of displaying suicidal phenomena and differ considerably to adolescents in this regard.

Computed radiography (CR) and digital radiography (DR) are replacing traditional film screen radiography as hospitals move towards digital imaging and picture archiving and communication systems (PACS). Both IPEM and KCARE have recently published quality assurance and acceptance testing guidelines for DR. In this paper, the performance of a range of CR and DR systems is compared. Six different manufacturers are included. Particular attention is paid to the performance of the systems under automatic exposure control (AEC). The patient is simulated using a range of thicknesses of tissue equivalent material. Image quality assessment was based on detector assessment protocols and includes pixel value measures as well as subjective assessment using Leeds Test Objects. The protocols for detector assessment cover a broad range of tests and in general detectors (whether DR or CR) performed satisfactorily. The chief limitation in performing these tests was that not all systems provided ready access to pixel values. Subjective tests include the use of the Leeds TO20. As part of this work, suggested reference values are provided to calculate the TO20 image quality factor. One consequence of moving from film screen to digital technologies is that the dynamic range of digital detectors is much wider, and increased exposures are no longer evident from changes in image quality. As such, AEC is a key parameter for CR and DR. Dose was measured using a standard phantom as a basic means of comparing systems. In order to assess the AEC performance, exit doses were also measured while varying phantom thickness. Signal-to-noise ratios (SNRs) were calculated on a number of systems where pixel values were available. SNR was affected by the selection of acquisition protocol. Comparisons between different technologies and collation of data will help refine acceptance thresholds and contribute to optimising dose and image quality.