Type I and III interferons (IFNs) activate similar downstream signaling cascades, but unlike type I IFNs, type III IFNs (IFNl) do not elicit strong inflammatory responses in vivo. Here, we examined the molecular mechanisms underlying this disparity. Type I and III IFNs displayed kinetic differences in expression of IFN-stimulated genes and proinflammatory responses, with type I IFNs preferentially stimulating expression of the transcription factor IRF1. Type III IFNs failed to induce IRF1 expression because of low IFNl receptor abundance and insufficient STAT1 activation on epithelial cells and thus did not activate the IRF1 proinflammatory gene program. Rather, IFNl stimulation preferentially induced factors implicated in tissue repair. Our findings suggest that IFN receptor compartmentalization and abundance confer a spatiotemporal division of labor where type III IFNs control viral spread at the site of the infection while restricting tissue damage; the transient induction of inflammatory responses by type I IFNs recruits immune effectors to promote protective immunity.

SUMMARY Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17raΔK13). Following oral Candida infection, Il17raΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra−/− mice. Susceptibility in Il17raΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3−/− mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3expression.

Clinical observations link respiratory virus infection and Pseudomonas aeruginosa colonization in chronic lung disease, including cystic fibrosis (CF) and chronic obstructive pulmonary disease. The development of P. aeruginosa into highly antibiotic-resistant biofilm communities promotes airway colonization and accounts for disease progression in patients. Although clinical studies show a strong correlation between CF patients' acquisition of chronic P. aeruginosa infections and respiratory virus infection, little is known about the mechanism by which chronic P. aeruginosa infections are initiated in the host. Using a coculture model to study the formation of bacterial biofilm formation associated with the airway epithelium, we show that respiratory viral infections and the induction of antiviral interferons promote robust secondary P. aeruginosa biofilm formation. We report that the induction of antiviral IFN signaling in response to respiratory syncytial virus (RSV) infection induces bacterial biofilm formation through a mechanism of dysregulated iron homeostasis of the airway epithelium. Moreover, increased apical release of the host iron-binding protein transferrin during RSV infection promotes P. aeruginosa biofilm development in vitro and in vivo. Thus, nutritional immunity pathways that are disrupted during respiratory viral infection create an environment that favors secondary bacterial infection and may provide previously unidentified targets to combat bacterial biofilm formation.respiratory syncytial virus | nutritional immunity | cystic fibrosis | Pseudomonas aeruginosa | biofilm

(2,4,7,9,10). B cell-deficient mice display enhanced susceptibility to M. tuberculosis, as assessed by tissue bacterial burden (4, 11), which is associated with aberrant lung cytokine (4) and granulomatous inflammatory response (4, 12, 13), as well as tissue neutrophilia (4, 13). Of note, there is evidence suggesting that the inflammation regulatory role of B cells during M. tuberculosis infection can be strain and infection phase specific (4, 12, 13). Studies using specific Fc␥ receptor knockout mouse strains have shown that signaling through distinct receptors can differentially regulate susceptibility to M. tuberculosis, as measured by tissue bacterial load, and lung cytokine production, suggesting a role for immunoglobulins in regulating the immune response to the pathogen (14). Indeed, enhanced susceptibility to M. tuberculosis that is associated with aberrant lung cytokine production has been observed in agammaglobulinemic AID Ϫ/Ϫ S Ϫ/Ϫ mice (15). Treatment with a number of monoclonal antibodies against specific mycobacterial components has been shown to be protective against challenge with M. tuberculosis (16), and coating M. tuberculosis bacilli with a monoclonal antibody of the IgG3 isotype against arabinomannan attenuated virulence relative to uncoated bacilli (17).The present study explored the effects of B cell depletion in the cynomolgus macaque model of tuberculosis (TB) (18,19). Cynomolgus macaques recapitulate the full infection outcome and pathological spectrum of M. tuberculosis infection seen in humans. Like humans, macaques are extremely variable in their response to M. tuberculosis infection, with substantial animal-toanimal and within-animal variability in terms of immune responses and bacterial numbers. We published previously that CFU per granuloma varied from 0 to 10 5 within individual animals, and T cell responses were equally variable in granulomas from an individual animal. This variability suggests that local mechanisms of control of infection, and the immune responses necessary for control of M. tuberculosis differ from granuloma to

An XTREME Technologies XTS 13-35 extreme ultraviolet (EUV) light source creates a xenon z pinch that generates 13.5nm light. Due to the near x-ray nature of light at this wavelength, extremely smooth metal mirrors for photon collection must be employed. These are exposed to the source debris. Dissolution of the z-pinch gas column results in high-energy ion and neutral release throughout the chamber that can have adverse effects on mirror surfaces. The XTREME commercial EUV emission diagnostic chamber was designed to maximize diagnostic access to the light and particulate emissions from the z pinch. The principal investigation is characterization of the debris field and the erosive effects on optics present. Light emission from the z pinch is followed by ejection of multiply charged ions and fast neutral particles that make up an erosive flux to chamber surfaces. Attenuation of this erosive flux to optical surfaces is attempted by inclusion of a debris mitigation tool consisting of foil traps and neutral buffer gas flow. Characterization of the z-pinch ejecta is performed with a spherical sector energy analyzer (ESA) that diagnoses fast ion species by energy-to-charge ratio using ion time-of-flight (ITOF) analysis. This is used to evaluate the debris tool’s ability to divert direct fast ions from impact on optic surfaces. The ITOF-ESA is used to characterize both the energy and angular distribution of the direct fast ions. Xe+ up to Xe+4 ions have been characterized along with Ar+ (the buffer gas used), W+, Mo+, Si+, Fe+, and Ni+. Energy spectra for these species from 0.5 up to 13keV are defined at 20° and 30° from the pinch centerline in the chamber. Results show a drop in ion flux with angular increase. The dominant species is Xe+ which peaks around 8keV. Ion flux measured against buffer gas flow rate suggests that the direct fast ion population is significantly attenuated through increases in buffer gas flow rate. This does not address momentum transfer from scattered ions or fast neutral particles. These results are discussed in the context of other investigations on the effects of total particle flux to normal incidence mirror samples exposed for 1×107 pulses. The samples (Si∕Mo multilayer with Ru capping layer, Au, C, Mo, Pd, Ru, and Si) were exposed to the source plasma with 75% argon flow rate in the debris mitigation tool and surface metrology was performed using x-ray photoelectron spectroscopy, atomic force microscopy, x-ray reflectivity, and scanning electron microscopy to analyze erosion effects on mirrors. These results are compared to the measured direct ion debris field.

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The Interaction of Materials with Particles and Components Testing (IMPACT) experimental facility is furnished with multiple ion sources and in situ diagnostics to study the modification of surfaces undergoing physical, chemical, and electronic changes during exposure to energetic particle beams. Ion beams with energies in the range between 20 and 5000 eV can bombard samples at flux levels in the range of 10(10)-10(15) cm(-2) s(-1); parameters such as ion angle of incidence and exposed area are also controllable during the experiment. IMPACT has diagnostics that allow full characterization of the beam, including a Faraday cup, a beam imaging system, and a retarding field energy analyzer. IMPACT is equipped with multiple diagnostics, such as electron (Auger, photoelectron) and ion scattering spectroscopies that allow different probing depths of the sample to monitor compositional changes in multicomponent and/or layered targets. A unique real-time erosion diagnostic based on a dual quartz crystal microbalance measures deposition from an eroding surface with rates smaller than 0.01 nm/s, which can be converted to a sputter yield measurement. The monitoring crystal can be rotated and placed in the target position so that the deposited material on the quartz crystal oscillator surface can be characterized without transfer outside of the vacuum chamber.

Ti and TiN films are used as diffusion barrier layers in Al and Cu metallization. They are often produced using physical-vapor-deposition techniques and are subject to energetic particle bombardment during subsequent processes. Therefore, the sputtering yield for ion-induced physical sputtering is important. The absolute sputtering yields of Ti and TiN target materials with 400-700 eV normally incident N and Ar ions are measured here. The experimental values are favorably compared to simulation results from TRIM.SP, which is a vectorized Monte Carlo code simulating ion-surface interaction using a binary collision mode. The phenomenon of reactive sputtering of Ti with incident N is also discussed.