Murine fecal microbiota transplantation lowers gastrointestinal pathogen loads and dampens pro-inflammatory immune responses in Campylobacter jejuni infected secondary abiotic mice

Conventional mice are protected from Campylobacter jejuni infection by the murine host-specific gut microbiota composition. We here addressed whether peroral fecal microbiota transplantation (FMT) might be an antibiotics-independent option to lower even high gastrointestinal C. jejuni loads in the infected vertebrate host. To address this, secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally infected with C. jejuni by gavage. One week later, mice were stably colonized with more than 109 C. jejuni and subjected to peroral FMT from murine donors on three consecutive days. Two weeks post-intervention, gastrointestinal C. jejuni loads were up to 7.5 orders of magnitude lower following murine FMT versus mock challenge. Remarkably, FMT reversed C. jejuni induced colonic epithelial apoptosis, but enhanced proliferative and regenerative responses in the colon thereby counteracting pathogenic cell damage. Furthermore, FMT dampened both, innate and adaptive immune cell responses in the large intestines upon C. jejuni infection that were accompanied by less C. jejuni-induced colonic nitric oxide secretion. Our study provides strong evidence that novel probiotic formulations developed as alternative option to FMT in severe intestinal inflammatory morbidities including Clostridoides difficile infection might be effective to treat campylobacteriosis and lower pathogen loads in colonized vertebrates including farm animals

Murine Fecal Microbiota Transplantation Alleviates Intestinal and Systemic Immune Responses in Campylobacter jejuni Infected Mice Harboring a Human Gut Microbiota

Human campylobacteriosis constitutes a zoonotic food-borne disease and a progressively rising health burden of significant socioeconomic impact. We have recently shown that conventional mice are protected from Campylobacter jejuni infection, which was not the case for human microbiota associated (hma) mice indicating that the host-specific gut microbiota composition primarily determines susceptibility to or resistance against C. jejuni infection. In our present preclinical intervention study we addressed whether gut microbiota changes in stably C. jejuni infected hma mice following murine fecal microbiota transplantation (mFMT) could alleviate pathogen-induced immune responses. To accomplish this, secondary abiotic C57BL/6 mice were generated by broad-spectrum antibiotic treatment, perorally reassociated with a complex human gut microbiota and challenged with C. jejuni by gavage. Seven days later C. jejuni infected hma mice were subjected to peroral mFMT on 3 consecutive days. Within a week post-mFMT fecal pathogenic burdens had decreased by two orders of magnitude, whereas distinct changes in the gut microbiota composition with elevated numbers of lactobacilli and bifidobacteria could be assessed. In addition, mFMT resulted in less C. jejuni induced apoptotic responses in colonic epithelia, reduced numbers of macrophages and monocytes as well as of T lymphocytes in the large intestinal mucosa and lamina propria and in less distinct intestinal pro-inflammatory cytokine secretion as compared to mock challenge. Strikingly, inflammation dampening effects of mFMT were not restricted to the intestinal tract, but could also be observed systemically as indicated by elevated serum concentrations of pro-inflammatory cytokines such as TNF-α, IL-12p70, and IL-6 in C. jejuni infected hma mice of the mock, but not the mFMT cohort. In conclusion, our preclinical mFMT intervention study provides evidence that changes in the gut microbiota composition which might be achieved by pre- or probiotic formulations may effectively lower intestinal C. jejuni loads, dampen both, pathogen-induced intestinal and systemic inflammatory sequelae and may represent a useful tool to treat continuous shedding of C. jejuni by asymptomatic carriers which is critical in the context of food production, hospitalization and immunosuppression

The Other Natural Two Higgs Doublet Model

We characterize models where electroweak symmetry breaking is driven by two light Higgs doublets arising as pseudo-Nambu-Goldstone bosons of new dynamics above the weak scale. They represent the simplest natural two Higgs doublet alternative to supersymmetry. We construct their low-energy effective Lagrangian making only few specific assumptions about the strong sector. These concern their global symmetries, their patterns of spontaneous breaking and the sources of explicit breaking. In particular we assume that all the explicit breaking is associated with the couplings of the strong sector to the Standard Model fields, that is gauge and (proto)-Yukawa interactions. Under those assumptions the scalar potential is determined at lowest order by very few free parameters associated to the top sector. Another crucial property of our scenarios is the presence of a discrete symmetry, in addition to custodial SO(4), that controls the $T$-parameter. That can either be simple CP or a $Z_2$ that distinguishes the two Higgs doublets. Among various possibilities we study in detail models based on SO(6)/SO(4)$\times$ SO(2), focussing on their predictions for the structure of the scalar spectrum and the deviations of their couplings from those of a generic renormalizable two Higgs doublet model.Comment: 54 page

A new cross section measurement of reactions induced by 3He-particles on a carbon target

International audienceThe production of intense beams of light radioactive nuclei can be achieved at the SPIRAL2 facility using intense stable beams accelerated by the driver accelerator and impinging on light targets. The isotope 14O is identied to be of high interest for future experiments. The excitation function of the production reaction 12C(3He, n)14O was measured between 7 and 35 MeV. Results are compared with literature data. As an additional result, we report the rst cross-section measurement for the 12C(3He, +n)10C reaction. Based on this new result, the potential in-target 14O yield at SPIRAL2 was estimated: 2.4x1011 pps, for 1 mA of 3He at 35 MeV. This is a factor 140 higher than the in-target yield at SPIRAL1

In vitro pharmacoregulation of CC chemokine ligand 5 and its receptor CCR5 in diffuse lung diseases.

BACKGROUND: CC chemokine ligand (CCL)5 and its receptor CCR5 contribute to leukocyte migration into lungs of patients with diffuse lung diseases (DLD). Pharmacological regulation of CCL5 and CCR5 expression was therefore explored in bronchoalveolar cells obtained from patients with DLD. METHODS: Cells from 21 patients were co-cultivated in vitro with tumour necrosis factor-alpha and dexamethasone, cyclosporin A (CyA) or pentoxifylline. Chemokine mRNA expression and protein production was assessed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Dexamethasone altered CCL5 mRNA expression and suppressed its protein levels. CyA inhibited chemokine mRNA expression but not protein production. Pentoxifylline did not affected chemokine expression. Both dexamethasone and CyA suppressed CCR5 mRNA transcripts. CONCLUSION: In conclusion, while dexamethasone downregulates the CCL5 functional form, CyA and pentoxifylline have no effects on CCL5 protein. These data provide in vitro correlation for clinical applications of immunomodulators in therapy of DLD

Measurement of the 20 and 90 keV resonances in the 18O(p,α)15{}^{18}{\rm O}(p,\alpha){}^{15}N reaction via THM

The $^{18}{\rm O}(p,\alpha)^{15}{\rm N}$ reaction is of primary importance in several astrophysical scenarios, including fluorine nucleosynthesis inside AGB stars as well as oxygen and nitrogen isotopic ratios in meteorite grains. Thus the indirect measurement of the low energy region of the $^{18}{\rm O}(p,\alpha)^{15}{\rm N}$ reaction has been performed to reduce the nuclear uncertainty on theoretical predictions. In particular the strength of the 20 and 90 keV resonances have been deduced and the change in the reaction rate evaluated.Comment: 4 pages, 4 figures, submitted to PR

Unveiling the intruder deformed 02+^+_2 state in 34^{34}Si

The 0$^+_2$ state in $^{34}$Si has been populated at the {\sc Ganil/Lise3} facility through the $\beta$-decay of a newly discovered 1$^+$ isomer in $^{34}$Al of 26(1) ms half-life. The simultaneous detection of $e^+e^-$ pairs allowed the determination of the excitation energy E(0$^+_2$)=2719(3) keV and the half-life T$_{1/2}$=19.4(7) ns, from which an electric monopole strength of $\rho^2$(E0)=13.0(0.9)$\times10^{-3}$ was deduced. The 2$^+_1$ state is observed to decay both to the 0$^+_1$ ground state and to the newly observed 0$^+_2$ state (via a 607(2) keV transition) with a ratio R(2$^+_1$$\rightarrow0^+_1/2^+_1$$\rightarrow0^+_2$)=1380(717). Gathering all information, a weak mixing with the 0$^+_1$ and a large deformation parameter of $\beta$=0.29(4) are found for the 0$^+_2$ state, in good agreement with shell model calculations using a new {\sc sdpf-u-mix} interaction allowing \textit{np-nh} excitations across the N=20 shell gap.Comment: 5 pages, 3 figures, accepted for publication in Physical Review Letter