Novel Murine Infection Models Provide Deep Insights into the “Ménage à Trois” of Campylobacter jejuni, Microbiota and Host Innate Immunity

BACKGROUND: Although Campylobacter jejuni-infections have a high prevalence worldwide and represent a significant socioeconomic burden, it is still not well understood how C. jejuni causes intestinal inflammation. Detailed investigation of C. jejuni-mediated intestinal immunopathology is hampered by the lack of appropriate vertebrate models. In particular, mice display colonization resistance against this pathogen. METHODOLOGY/PRINCIPAL FINDINGS: To overcome these limitations we developed a novel C. jejuni-infection model using gnotobiotic mice in which the intestinal flora was eradicated by antibiotic treatment. These animals could then be permanently associated with a complete human (hfa) or murine (mfa) microbiota. After peroral infection C. jejuni colonized the gastrointestinal tract of gnotobiotic and hfa mice for six weeks, whereas mfa mice cleared the pathogen within two days. Strikingly, stable C. jejuni colonization was accompanied by a pro-inflammatory immune response indicated by increased numbers of T- and B-lymphocytes, regulatory T-cells, neutrophils and apoptotic cells, as well as increased concentrations of TNF-α, IL-6, and MCP-1 in the colon mucosa of hfa mice. Analysis of MyD88(-/-), TRIF(-/-), TLR4(-/-), and TLR9(-/-) mice revealed that TLR4- and TLR9-signaling was essential for immunopathology following C. jejuni-infection. Interestingly, C. jejuni-mutant strains deficient in formic acid metabolism and perception induced less intestinal immunopathology compared to the parental strain infection. In summary, the murine gut flora is essential for colonization resistance against C. jejuni and can be overcome by reconstitution of gnotobiotic mice with human flora. Detection of C. jejuni-LPS and -CpG-DNA by host TLR4 and TLR9, respectively, plays a key role in immunopathology. Finally, the host immune response is tightly coupled to bacterial formic acid metabolism and invasion fitness. CONCLUSION/SIGNIFICANCE: We conclude that gnotobiotic and "humanized" mice represent excellent novel C. jejuni-infection and -inflammation models and provide deep insights into the immunological and molecular interplays between C. jejuni, microbiota and innate immunity in human campylobacteriosis

Deep-Sea Nematodes Actively Colonise Sediments, Irrespective of the Presence of a Pulse of Organic Matter: Results from an In-Situ Experiment

A colonisation experiment was performed in situ at 2500 m water depth at the Arctic deep-sea long-term observatory HAUSGARTEN to determine the response of deep-sea nematodes to disturbed, newly available patches, enriched with organic matter. Cylindrical tubes,laterally covered with a 500 µm mesh, were filled with azoic deep-sea sediment and 13C-labelled food sources (diatoms and bacteria). After 10 days of incubation the tubes were analysed for nematode response in terms of colonisation and uptake. Nematodes actively colonised the tubes,however with densities that only accounted for a maximum of 2.13% (51 ind.10 cm−2) of the ambient nematode assemblages. Densities did not differ according to the presence or absence of organic matter, nor according to the type of organic matter added. The fact that the organic matter did not function as an attractant to nematodes was confirmed by the absence of notable 13C assimilation by the colonising nematodes. Overall, colonisationappears to be a process that yields reproducible abundance and diversity patterns, with certain taxa showing more efficiency. Together with the high variability between the colonising nematode assemblages, this lends experimental support to the existence of a spatio-temporal mosaic that emerges from highly localised, partially stochastic community dynamics

Continuous Flow of Upper Labrador Sea Water around Cape Hatteras

Abstract Six velocity sections straddling Cape Hatteras show a deep counterflow rounding the Cape wedged beneath the poleward flowing Gulf Stream and the continental slope. This counterflow is likely the upper part of the equatorward-flowing Deep Western Boundary Current (DWBC). Hydrographic data suggest that the equatorward flow sampled by the shipboard 38 kHz ADCP comprises the Upper Labrador Sea Water (ULSW) layer and top of the Classical Labrador Sea Water (CLSW) layer. Continuous DWBC flow around the Cape implied by the closely-spaced velocity sections here is also corroborated by the trajectory of an Argo float. These findings contrast with previous studies based on floats and tracers in which the lightest DWBC constituents did not follow the boundary to cross under the Gulf Stream at Cape Hatteras but were diverted into the interior as the DWBC encountered the Gulf Stream in the crossover region. Additionally, our six quasi-synoptic velocity sections confirm that the Gulf Stream intensified markedly at that time as it approached the separation point and flowed into deeper waters. Downstream increases were observed not only in the poleward transport across the sections but also in the current’s maximum speed

Source study of 2017 Hojedk triplet earthquake sequence, southeast Iran

In December 2017, a triplet earthquake sequence of M(w)5.8-6.1 occurred near Hojedk, southeast Iran. The sequence was not destructive, but occurred in a highly seismically active region that previously experienced the 1981-1998 Sirch-Golbaf earthquake sequence and destructive 2003 M(w)6.6 Bam earthquake. We apply a waveform inversion method based on the modeling of regional seismic broadband data to derive the point source and kinematic rupture parameters of the triplet and its five significant aftershocks. The choice of an earthquake source model with a reduced number of parameters and a sequential inversion process with several iterations result in unique and stable earthquake source solutions. Within the inversion process, we combine the modeling of low- and high-frequency seismological data to retrieve the moment tensor and the kinematic source parameters. Synthetic seismogram and spectra are generated for an accurate regional velocity model. Our results suggest that the triplet ruptured a segmented fault system, with centroid locations aligned along a single lineament. Estimation of rupture directivity suggests the activation of SE-NW structure. In conclusion, we suggest that the triplet was associated with the failure of one or more aligned blind thrust faults, oriented SE-NW and dipping to the NE, in a restraining bend between strike-slip faults in a region that is a part of the greater system of the present continental shortening in Iran.</p