Heme oxygenase-1 is a critical regulator of nitric oxide production in enterohemorrhagic Escherichia coli-infected human enterocytes

Enterohemorrhagic Escherichia coli (EHEC) are the causative agent of hemolytic-uremic syndrome. In the first stage of the infection, EHEC interact with human enterocytes to modulate the innate immune response. Inducible NO synthase (iNOS)-derived NO is a critical mediator of the inflammatory response of the infected intestinal mucosa. We therefore aimed to analyze the role of EHEC on iNOS induction in human epithelial cell lines. In this regard, we show that EHEC down-regulate IFN-gamma-induced iNOS mRNA expression and NO production in Hct-8, Caco-2, and T84 cells. This inhibitory effect occurs through the decrease of STAT-1 activation. In parallel, we demonstrate that EHEC stimulate the rapid inducible expression of the gene hmox-1 that encodes for the enzyme heme oxygenase-1 (HO-1). Knock-down of hmox-1 gene expression by small interfering RNA or the blockade of HO-1 activity by zinc protoporphyrin IX abrogated the EHEC-dependent inhibition of STAT-1 activation and iNOS mRNA expression in activated human enterocytes. These results highlight a new strategy elaborated by EHEC to control the host innate immune response.

Wgamma production and limits on anomalous WWgamma couplings in ppbar collisions

We measure the cross section and the difference in rapidities between photons and charged leptons for inclusive W -> lnu+gamma production in egamma and mugamma final states. Using data corresponding to an integrated luminosity of 4.2 fb-1 collected with the D0 detector at the Fermilab Tevatron Collider, the cross section multiplied by the branching fraction for the process ppbar -> Wgamma+X -> lnugamma+X, measured to be 15.8 +/- 0.8 (stat.) +/- 1.2 (syst.) pb, and the distribution of the charge-signed photon-lepton rapidity difference are found to be in agreement with the standard model. These results provide the most stringent limits on anomalous WWgamma couplings for data from hadron colliders: -0.4 < Delta kappa_gamma < 0.4 and -0.08 < lambda_gamma < 0.07 at the 95% C.L.

Measurement of the cross-section for W boson production in association with b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

This paper reports a measurement of the W+b-jets (W+b+X and W+b (b) over bar +X) production cross-section in proton-proton collisions at a centre-of-mass energy of 7 TeV at the LHC. These results are based on data corresponding to an integrated luminosity of 4.6 fb(-1), collected with the ATLAS detector. Cross-sections are presented as a function of jet multiplicity and of the transverse momentum of the leading b-jet for both the muon and electron decay modes of the W boson. The W+b-jets cross-section, corrected for all known detector effects, is quoted in a limited kinematic range. Combining the muon and electron channels, the fiducial cross-section for W+b-jets is measured to be 7.1 +/- 0.5 (stat) +/- 1.4 (syst) pb, consistent with the next-to-leading order QCD prediction, corrected for non-perturbative and double-parton interactions (DPI) contributions, of 4.70 +/- 0.09 (stat) (+0.60)(-0.49) (scale) +/- 0.06 (PDF) +/- 0.16 (non-pert) (+0.52)(-0.38) (DPI) pb.

Measurement of the total cross section from elastic scattering in pp collisions at √s=7TeV with the ATLAS detector

A measurement of the total pp cross section at the LHC at √s = 7 TeV is presented. In a special run with high-β* beam optics, an integrated luminosity of 80 μb−1 was accumulated in order to measure the differential elastic cross section as a function of the Mandelstam momentum transfer variable t . The measurement is performed with the ALFA sub-detector of ATLAS. Using a fit to the differential elastic cross section in the |t | range from 0.01 GeV2 to 0.1 GeV2 to extrapolate to |t | →0, the total cross section, σtot(pp→X), is measured via the optical theorem to be: σtot(pp→X) = 95.35± 0.38 (stat.)± 1.25 (exp.)± 0.37 (extr.) mb, where the first error is statistical, the second accounts for all experimental systematic uncertainties and the last is related to uncertainties in the extrapolation to |t | → 0. In addition, the slope of the elastic cross section at small |t | is determined to be B = 19.73 ±0.14 (stat.) ±0.26 (syst.) GeV−2.

Study of heavy-flavor quarks produced in association with top-quark pairs at s √ =7 TeV using the ATLAS detector

Using a sample of dilepton top-quark pair (tt ¯ ) candidate events, a study is performed of the production of top-quark pairs together with heavy-flavor (HF) quarks, the sum of tt ¯ +b+X and tt ¯ +c+X , collectively referred to as tt ¯  + HF . The data set used corresponds to an integrated luminosity of 4.7  fb −1 of proton-proton collisions at a center-of-mass energy of 7 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. The presence of additional HF (b or c ) quarks in the tt ¯ sample is inferred by looking for events with at least three b -tagged jets, where two are attributed to the b quarks from the tt ¯ decays and the third to additional HF production. The dominant background to tt ¯  + HF in this sample is tt ¯ +jet events in which a light-flavor jet is misidentified as a heavy-flavor jet. To determine the heavy- and light-flavor content of the additional b -tagged jets, a fit to the vertex mass distribution of b -tagged jets in the sample is performed. The result of the fit shows that 79 ± 14 (stat) ± 22 (syst) of the 105 selected extra b -tagged jets originate from HF quarks, 3 standard deviations away from the hypothesis of zero tt ¯  + HF production. The result for extra HF production is quoted as a ratio (R HF ) of the cross section for tt ¯  + HF production to the cross section for tt ¯ production with at least one additional jet. Both cross sections are measured in a fiducial kinematic region within the ATLAS acceptance. R HF is measured to be [6.2±1.1(stat)±1.8(syst)]% for jets with p T >25  GeV and |η|<2.5 , in agreement with the expectations from Monte Carlo generators.

Measurement of the νμ charged current quasielastic cross section on carbon with the T2K on-axis neutrino beam

We report a measurement of the νµ charged current quasi-elastic cross-sections on carbon in the T2K on-axis neutrino beam. The measured charged current quasi-elastic cross-sections on carbon at mean neutrino energies of 1.94 GeV and 0.93 GeV are (11.95 ± 0.19(stat.) +1.82−1.47(syst.)) ×10^−39 cm^2/neutron, and (10.64 ± 0.37(stat.)+2.03−1.65(syst.)) × 10^−39 cm^2/neutron, respectively. These results agree well with the predictions of neutrino interaction models. In addition, we investigated the effects of the nuclear model and the multi-nucleon interaction.

Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33

In mice, interleukin-18 (IL-18) regulates Th1- or Th2-type immune responses depending on the cytokine environment and effector cells involved, and the ST2-ligand, IL-33, primarily promotes an allergic phenotype. Human basophils, major players in allergic inflammation, constitutively express IL-18 receptors, while ST2 surface expression is inducible by IL-3. Unexpectedly, freshly isolated basophils are strongly activated by IL-33, but, in contrast to mouse basophils, do not respond to IL-18. IL-33 promotes IL-4, IL-13 and IL-8 secretion in synergy with IL-3 and/or FcepsilonRI-activation, and enhances FcepsilonRI-induced mediator release. These effects are similar to that of IL-3, but the signaling pathways engaged are distinct because IL-33 strongly activates NF-kappaB and shows a preference for p38 MAP-kinase, while IL-3 acts through Jak/Stat and preferentially activates ERK. Eosinophils are the only other leukocyte-type directly activated by IL-33, as evidenced by screening of p38-activation in peripheral blood cells. Only upon CD3/CD28-ligation, IL-33 weakly enhances Th2 cytokine expression by in vivo polarized Th2 cells. This study on primary human cells demonstrates that basophils and eosinophils are the only direct target leukocytes for IL-33, suggesting that IL-33 promotes allergic inflammation and Th2 polarization mainly by the selective activation of these specialized cells of the innate immune system.

Co-activation of JAK/STAT and p38 MAPK pathways by type I interferon enhances apoptosis in human basophils

It has previously been published that interferon-α (type I IFN) improves clinical symptoms of asthma patients. Since human basophils are major inflammatory cells in maintaining chronic allergic asthma we investigate whether type I IFN affect human blood basophils. Furthermore, previous studies have shown that spontaneous apoptosis of human basophils is slow due to constitutive expression of anti-apoptotic BCL-2 family members. In addition, IL-3 exceptionally promotes survival of basophils by enhancing constitutive expression of BCL-2 family members and by inducing de-novo expression of Pim-1 kinase. Thus, we also assessed whether type I IFN might overcome IL-3-induced survival of human basophils. Our data show that type I IFN enhances apoptosis in purified human blood basophils compared to spontaneous apoptosis of controls or type II IFN treated cells. Furthermore, we demonstrate that both type I IFN and FasL enhance apoptosis in human basophils with similar efficiency in a rather additive than synergistic way. Analyses of signaling pathways reveal that type I IFN promote prolonged phosphorylation of STAT1/STAT2. By using a pan-JAK inhibitor the phosphorylation of STAT1/STAT2 is inhibited and most importantly the pro-apoptotic effect of type I IFN is abolished. On the other hand, type I IFN do not reduce IL-3-induced de novo expression of Pim-1 and BCL-2. This is in line with our observation that IL-3-induced survival is dominant over type I IFN-enhanced apoptosis. In addition, phosphorylation of p38 MAPK in type I IFN treated cells is comparable to non-treated cells. Particularly however, inhibition of this p-p38 activity abrogates apoptosis as well. We conclude that type I IFN-enhanced apoptosis is tightly regulated by the cooperation of JAK/STAT and p38 MAPK pathways. Our study identifies a so far unknown effect of type I IFN and may explain the improved clinical symptoms of asthma patients treated with type I IFN.