Proteolytic homeostasis is important at mucosal surfaces, but its actors and their precise role in physiology are poorly understood. Here we report that healthy human and mouse colon epithelia are a ...major source of active thrombin. We show that mucosal thrombin is directly regulated by the presence of commensal microbiota. Specific inhibition of luminal thrombin activity causes macroscopic and microscopic damage as well as transcriptomic alterations of genes involved in host-microbiota interactions. Further, luminal thrombin inhibition impairs the spatial segregation of microbiota biofilms, allowing bacteria to invade the mucus layer and to translocate across the epithelium. Thrombin cleaves the biofilm matrix of reconstituted mucosa-associated human microbiota. Our results indicate that thrombin constrains biofilms at the intestinal mucosa. Further work is needed to test whether thrombin plays similar roles in other mucosal surfaces, given that lung, bladder and skin epithelia also express thrombin.
The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2‐year‐old boy in Meliandou, Guinea. We investigated the zoonotic origins of the ...epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in a hollow tree housing a colony of insectivorous free‐tailed bats (Mops condylurus). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks, and experimental data have shown that this species can survive experimental infection. These analyses expand the range of possible Ebola virus sources to include insectivorous bats and reiterate the importance of broader sampling efforts for understanding Ebola virus ecology.
Synopsis
The severe Ebola virus disease epidemic occurring in West Africa likely stems from a single zoonotic transmission event involving a 2‐year‐old boy in Meliandou, Guinea, who might have been infected by hunting or playing with insectivorous free‐tailed bats living in a nearby hollow tree.
Monitoring data show that larger wildlife did not experience a recent decline and is therefore unlikely to have served as the source for the Ebola virus disease epidemic in West Africa.
Fruit bat hunting and butchering are common activities in southern Guinea, therefore facilitating direct human contact.
Children are also exposed to insectivorous bats through hunting in and around villages.
No large colony of fruit bats exists in or nearby the index village (Meliandou).
The 2‐year‐old index case may have been infected by playing in a hollow tree housing a colony of insectivorous free‐tailed bats (Mops condylurus).
The severe Ebola virus disease epidemic occurring in West Africa likely stems from a single zoonotic transmission event involving a 2‐year‐old boy in Meliandou, Guinea, who might have been infected by hunting or playing with insectivorous free‐tailed bats living in a nearby hollow tree.
Root knot nematodes are obligate phytoparasites that invade the roots of important crop plants causing severe economic losses. Arbuscular Mycorrhizal Fungi (AMF) are soil borne microorganisms that ...establish mutualistic associations with the roots of most plants. AMF have been frequently indicated to help their host to attenuate the damage caused by pathogens and predators. In this study, the effects of a commercial inoculum of AMF against Meloidogyne incognita on tomato and pepper were evaluated under controlled conditions. Mycorrhizal association decreased M. incognita development in pepper, and improved tolerance to nematode infection in tomato plants. Rapid plant mycorrhization is critical for delivering protective effects against biotic stress. A novel mycorrhization technique using AMF from the highly mycotrophic plant sorghum was applied to tomato. More rapid mycorrhization was achieved in tomato plants grown in soil containing mycorrhized roots of sorghum than in plants directly inoculated with the commercial AMF. Keywords. Crop pests, symbiosis, agricultural management.
Elucidating mechanisms involved in tumor-induced immunosuppression is of great interest since it could help to improve cancer immunotherapy efficacy. Here we show that Hepatocyte Growth Factor (HGF), ...a pro-tumoral and proangiogenic factor, and its receptor c-Met are involved in regulatory T cells (Treg) accumulation in the peripheral blood of gastric cancer (GC) patients. We observed that c-Met is expressed on circulating monocytes from GC patients. The elevated expression on monocytes is associated with clinical parameters linked to an aggressive disease phenotype and correlates with a worse prognosis. Monocyte-derived dendritic cells from GC patients differentiated in the presence of HGF adopt a regulatory phenotype with a lower expression of co-stimulatory molecules, impaired maturation capacities, and an increased ability to produce interleukin-10 and to induce Treg differentiation in vitro. In the MEGA-ACCORD20-PRODIGE17 trial, GC patients received an anti-HGF antibody treatment (rilotumumab), which had been described to have an anti-angiogenic activity by decreasing proliferation of endothelial cells and tube formation. Rilotumumab decreased circulating Treg in GC patients. Thus, we identified that HGF indirectly triggers Treg accumulation via c-Met-expressing monocytes in the peripheral blood of GC patients. Our study provides arguments for potential alternative use of HGF/c-Met targeted therapies based on their immunomodulatory properties which could lead to the development of new therapeutic associations in cancer patients, for example with immune checkpoint inhibitors.
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