Dendritic Cells in Chronic Mycobacterial Granulomas Restrict Local Anti-Bacterial T Cell Response in a Murine Model

Background: Mycobacterium-induced granulomas are the interface between bacteria and host immune response. During acute infection dendritic cells (DCs) are critical for mycobacterial dissemination and activation of protective T cells. However, their role during chronic infection in the granuloma is poorly understood. Methodology/Principal Findings: We report that an inflammatory subset of murine DCs are present in granulomas induced by Mycobacteria bovis strain Bacillus Calmette-guerin (BCG), and both their location in granulomas and costimulatory molecule expression changes throughout infection. By flow cytometric analysis, we found that CD11c + cells in chronic granulomas had lower expression of MHCII and co-stimulatory molecules CD40, CD80 and CD86, and higher expression of inhibitory molecules PD-L1 and PD-L2 compared to CD11c + cells from acute granulomas. As a consequence of their phenotype, CD11c + cells from chronic lesions were unable to support the reactivation of newly-recruited, antigen 85Bspecific CD4 + IFNc + T cells or induce an IFNc response from naïve T cells in vivo and ex vivo. The mechanism of this inhibition involves the PD-1:PD-L signaling pathway, as ex vivo blockade of PD-L1 and PD-L2 restored the ability of isolated CD11c + cells from chronic lesions to stimulate a protective IFNc T cell response. Conclusions/Significance: Our data suggest that DCs in chronic lesions may facilitate latent infection by down-regulating protective T cell responses, ultimately acting as a shield that promotes mycobacterium survival. This DC shield may explai

High resolutionQ−1estimation based on extension of coda normalization method and its application toP-wave attenuation structure in the aftershock area of the 2005 West Off Fukuoka Prefecture Earthquake (M7.0)

We developed a method for estimating the seismic-wave attenuation (1/Q) in a seismically active region such as an aftershock area. To estimate the attenuation factor between two adjacent hypocentres, we employed two seismograms recorded at a station and calculate the ratio between two power spectra of direct waves normalized by those in the coda for both the events. The coda normalization of the spectrum and the ratio between the two events minimize the possible influences of sources, sites, instruments and attenuation from the station to the hypocentral area. The 1/Q value can be estimated from the variation of the ratios of event pairs calculated at many stations for various traveltime differences between the even pairs. This method involves double-difference (DD) estimation from the logarithmic power spectra for estimating the 1/Q structure, employing a concept similar to the recently developed ‘DD tomography’ for velocity structures. We applied this method to the aftershock area of the 2005 West Off Fukuoka Prefecture Earthquake (M7.0) in order to investigate the 1/Q structure of P waves. By using the spectra of the seismograms of 1781 events recorded at a dense seismic network deployed around the aftershock area, we obtained the spatial variation of the 1/Q value in this region. The 1/Q distribution thereby obtained suggests that there exists a high-attenuation region around the edge of the main shock fault, which could correspond to the segment boundary between the earthquake fault and the adjacent faults. In addition, we found that the initiation points of the main shock and aftershocks were located in a low-attenuation region