Marine transmissible cancer navigates urbanized waters, threatening spillover.

Inter-individual transmission of cancer cells represents a unique form of microparasites increasingly reported in marine bivalves. In this study, we sought to understand the ecology of the propagation of Mytilus trossulus Bivalve Transmissible Neoplasia 2 (MtrBTN2), a transmissible cancer affecting four Mytilus mussel species worldwide. We investigated the prevalence of MtrBTN2 in the mosaic hybrid zone of M. edulis and M. galloprovincialis along the French Atlantic coast, sampling contrasting natural and anthropogenic habitats. We observed a similar prevalence in both species, probably due to the spatial proximity of the two species in this region. Our results showed that ports had higher prevalence of MtrBTN2, with a possible hotspot observed at a shuttle landing dock. No cancer was found in natural beds except for two sites close to the hotspot, suggesting spillover. Ports may provide favourable conditions for the transmission of MtrBTN2, such as high mussel density, stressful conditions, sheltered and confined shores or buffered temperatures. Ships may also spread the disease through biofouling. Our results suggest ports may serve as epidemiological hubs, with maritime routes providing artificial gateways for MtrBTN2 propagation. This highlights the importance of preventing biofouling on docks and ship hulls to limit the spread of marine pathogens hosted by fouling species.

Transcriptomics of mussel transmissible cancer MtrBTN2 suggests accumulation of multiple cancer traits and oncogenic pathways shared among bilaterians.

Transmissible cancer cell lines are rare biological entities giving rise to diseases at the crossroads of cancer and parasitic diseases. These malignant cells have acquired the amazing capacity to spread from host to host. They have been described only in dogs, Tasmanian devils and marine bivalves. The Mytilus trossulus bivalve transmissible neoplasia 2 (MtrBTN2) lineage has even acquired the capacity to spread inter-specifically between marine mussels of the Mytilus edulis complex worldwide. To identify the oncogenic processes underpinning the biology of these atypical cancers we performed transcriptomics of MtrBTN2 cells. Differential expression, enrichment, protein-protein interaction network, and targeted analyses were used. Overall, our results suggest the accumulation of multiple cancerous traits that may be linked to the long-term evolution of MtrBTN2. We also highlight that vertebrate and lophotrochozoan cancers could share a large panel of common drivers, which supports the hypothesis of an ancient origin of oncogenic processes in bilaterians.

Traits of a mussel transmissible cancer are reminiscent of a parasitic life style.

Some cancers have evolved the ability to spread from host to host by transmission of cancerous cells. These rare biological entities can be considered parasites with a host-related genome. Still, we know little about their specific adaptation to a parasitic lifestyle. MtrBTN2 is one of the few lineages of transmissible cancers known in the animal kingdom. Reported worldwide, MtrBTN2 infects marine mussels. We isolated MtrBTN2 cells circulating in the hemolymph of cancerous mussels and investigated their phenotypic traits. We found that MtrBTN2 cells had remarkable survival capacities in seawater, much higher than normal hemocytes. With almost 100% cell survival over three days, they increase significantly their chances to infect neighboring hosts. MtrBTN2 also triggered an aggressive cancerous process: proliferation in mussels was ~ 17 times higher than normal hemocytes (mean doubling time of ~ 3 days), thereby favoring a rapid increase of intra-host population size. MtrBTN2 appears to induce host castration, thereby favoring resources re-allocation to the parasites and increasing the host carrying capacity. Altogether, our results highlight a series of traits of MtrBTN2 consistent with a marine parasitic lifestyle that may have contributed to the success of its persistence and dissemination in different mussel populations across the globe.

A systems biology analysis of the Drosophila phagosome.

Phagocytes have a critical function in remodelling tissues during embryogenesis and thereafter are central effectors of immune defence. During phagocytosis, particles are internalized into 'phagosomes', organelles from which immune processes such as microbial destruction and antigen presentation are initiated. Certain pathogens have evolved mechanisms to evade the immune system and persist undetected within phagocytes, and it is therefore evident that a detailed knowledge of this process is essential to an understanding of many aspects of innate and adaptive immunity. However, despite the crucial role of phagosomes in immunity, their components and organization are not fully defined. Here we present a systems biology analysis of phagosomes isolated from cells derived from the genetically tractable model organism Drosophila melanogaster and address the complex dynamic interactions between proteins within this organelle and their involvement in particle engulfment. Proteomic analysis identified 617 proteins potentially associated with Drosophila phagosomes; these were organized by protein-protein interactions to generate the 'phagosome interactome', a detailed protein-protein interaction network of this subcellular compartment. These networks predicted both the architecture of the phagosome and putative biomodules. The contribution of each protein and complex to bacterial internalization was tested by RNA-mediated interference and identified known components of the phagocytic machinery. In addition, the prediction and validation of regulators of phagocytosis such as the 'exocyst', a macromolecular complex required for exocytosis but not previously implicated in phagocytosis, validates this strategy. In generating this 'systems-based model', we show the power of applying this approach to the study of complex cellular processes and organelles and expect that this detailed model of the phagosome will provide a new framework for studying host-pathogen interactions and innate immunity.

Plasticity of adipose tissue: a promising therapeutic avenue in the treatment of cardiovascular and blood diseases?

The adipose tissue represents a large amount of adult tissues. For long time, it was considered as a poorly active overgrown and undesirable tissue even if its usefulness was demonstrated in reconstructive surgery. It was studied for its main involvement in energy metabolism and disorders as diabetes and obesity. More recently, its endocrine functions emerged and appeared to play a key role in many physiological situations such as inflammation and immunity. The presence of preadipocytes throughout life was demonstrated using primary culture technology from cells derived from adipose tissue. These cells can display a macrophagic or endothelial potential according to their environment and could be now considered as vascular progenitors. Differentiation of various adipose derived cell subsets towards functional cardiomyocytes, osteoblasts, haematopoietic and neural cells was also obtained in vitro. Altogether, these data emphasise the need to consider with a new look preadipocyte status and adipose tissue biology. These spectacular data, together with the fact that adipose tissue is easy to obtain lead to numerous and promising perspectives in regenerative medicine. They highlight the concept that progenitor cells from adipose tissue constitute an alternative for cells-based strategies designed for the treatment of cardiovascular diseases.

[Adipose tissue, plastic and reconstructive surgery: come back to sources]. / Tissus adipeux, chirurgie plastique et reconstructrice: le retour aux sources.

The adipose tissue represents a large amount of adult tissue. For long time, it was considered as a filling tissue and used in plastic and reconstructive surgery. It was always studied for its main involvement in energy metabolism and energy disorders as diabetes and obesity. More recently, its endocrine functions emerged and thus play a key role in many physiological functions as inflammation and immunity. The presence of preadipocytes throughout life was demonstrated using primary culture technology from cells derived from adipose tissue. In recent papers, cells derived from adipose tissue were used for haematopoiesis, vascularisation or skeletal muscle recovery. Differentiation into functional cardiomyocytes, osteoblasts and neural cells was obtained in vitro. These spectacular data, the fact that adipose tissue is easy to sample and the possibility to create cell or tissue banks open numerous and promising perspectives in regenerative medicine.

Bovine collagen induced systemic symptoms: antibody formation against bovine and human collagen.

We describe the first case of systemic symptoms after injection of bovine collagen and silicone polymers associated with antibodies to both native type I and II bovine and human collagen that varied with clinical features. Joint inflammation, edema at the injection site of bovine collagen implant and fever appeared 6 months after injection. Our patients history raises the question of whether the injection of animal derived collagen, particularly combined with silicone, induces or exacerbates autoimmune disease.

Assessment of the marker value of various components of the coli-aerogenes group of Enterobacteriaceae and of a selection of Enterococcus spp. for the official monitoring of drinking water supplies.

The traditional indicators Escherichia coli (in practice currently, though ecologically inaccurately, represented by 'thermotolerant coliforms' at 44 degrees C) and Enterococcus spp. proved to be suitable for the diagnosis of heavy and frequent faecal pollution observed in potentially dangerous waters, especially those originating from karstic aquifers. On the other hand, natural and treated waters, slightly and inconsistently contaminated, occasionally showed a variable Gram-negative flora, difficult to classify by routine tests. In that case, complete identification of isolates may be necessary to ensure a valid decision on the potability of the supply. At any rate some of the Enterobacteriaceae contained in the 'faecal coliform' group and many other 'coliforms', distinct from E. coli, lack sanitary significance although their presence at certain levels may indicate inadequate disinfection, hiatuses in the integrity of the distribution system or both.

Pro- and anti-inflammatory properties of human recombinant IL-1 beta during experimental arthritis in rats: 2. Period-dependent effect.

The systemic effects of human recombinant Interleukin-1 beta (HrIL-1 beta) on hindpaw edema were determined in arthritis induced by human native type II collagen (CII) with muramyl dipeptide (MDP) both injected on day 0. Daily treatment with HrIL-1 beta (0.2 microgram sc) pretreatment, from D-1 (the day before MDP and CII were injected) to D3 significantly delayed the secondary inflammation in the uninjected left hindpaw, whereas the same treatment from D6 to D10 at the end of the "primary" inflammation, enhanced the volume of the left hindpaw. Treatment from D13 to D17 did not affect the "secondary" edema in the left hindpaw. Thus, HrIL 1 beta administration produces pro- or anti-inflammatory effects on a developing polyarthritis depending on when treatment is started and is most effective as an anti-inflammatory molecule when started at the peak of the the inflammatory reaction, as previously described. In view of these early findings, we have compared the effect of adding HrIL-1 beta along with MDP in the sensitization procedure on the time-course of CII-induced arthritis. No adjuvant effect of HrIL-1 beta was observed. On the contrary, HrIL-1 beta significantly decreased the signs of inflammation in the injected hindpaw during the secondary inflammation. In addition, the immune response to type II collagen was less in the group receiving HrIL-1 beta, maybe because of nonspecific increase of antigen clearance. On the other hand, the MDP sensitization procedure enhanced the incidence of CII arthritis and significantly worsened the clinical parameters in both primary and secondary inflammations.

Immunoassay techniques for the detection of circulating antibodies to collagen following the use of collagen medical devices.

During the use of collagen medical devices, some adverse clinical reactions occur involving both the cellular and humoral types of the immune response. Thus, the development of immunoassay techniques for measuring the presence and the levels of circulating anticollagen antibodies is required. The authors present their protocol: it is a solid phase radioimmunoassay using collagen coated on polystyrene microplates and labelled protein A as the tracer. An example of the application of the technique is described. Anticollagen antibodies were monitored in 586 patients undergoing bovine collagen implant therapy. In a retrospective study on 166 patients we found a good correlation between the presence of antibodies to collagen and cellular immune reactions such as a positive skin test or adverse clinical reactions after implantation. A prospective study on 420 patients showed that the pretreatment anticollagen serologic test can be useful as an adjunct to skin testing in the conservative management of patients desiring bovine collagen implant therapy. The use of this double test allowed avoidance of any major clinical reaction and reduced minor signs of intolerance.

Influence of muramyl dipeptide on established experimental arthritis in rats.

The effects of MDP, a potent inducer of cytokines, were studied in four batches of Wistar Furth rats with established experimental arthritis. Arthritic rats were given a daily sc injection of 10, 100, 200 or 400 micrograms MDP respectively. Muramyl dipeptide increased the severity of clinical events in a dose-dependent manner, with the exception of the 10 micrograms dose which was ineffective. The levels of anti-collagen antibodies were not however significantly enhanced by MDP. Radiological lesions and histological changes were maximal at high dosage regimens. Paradoxically, the acute phase reactive alpha 1 glycoprotein was little affected by MDP treatment.

Lack of adjuvanticity of human recombinant interleukin-1 beta in collagen induced arthritis in rats.

We investigated the influence of human recombinant interleukin-1 beta (hrIL-1 beta) on the time-course of collagen induced arthritis (CIA) when injected concomitantly with the arthritogenic emulsion. Three sensitizing procedures were compared. The control group received type II collagen only. The other groups differed by the adjunction of demonstrated (MDP) or potential (IL-1 beta) adjuvant. No adjuvant effect of IL-1 was observed as judged on clinical or radiological scores. On the contrary, MDP significantly worsened the lesions of the injected right hindpaw, and increased the incidence of CIA. Surprisingly, humoral response to type II collagen was decreased in the group receiving IL-1 beta. This might be explained by a non specific increase of antigen clearance.

Tissue reaction to subcutaneous implantation of a collagen sponge. A histological, ultrastructural, and immunological study.

The biocompatibility of a subcutaneously implanted bovine collagen sponge (Haemostagen) was studied in rats by analyzing tissue reactions up to 3 months by histological and ultrastructural methods; in addition, the level of serum antibodies to bovine type I collagen (the major implant collagen) was measured by solid-phase radioimmunoassay. By 8 h after implantation, the implant was completely filled with polymorphonuclear cells (PMNs). After 8 days, fibroblasts had developed a granulation tissue within the sponge and the PMNs had almost disappeared. The small residue that remained after 1 month consisted of some densely packed collagen fibrils containing giant cells, which had disappeared by 3 months. No antibodies to bovine type I collagen were found in the sera of implanted rats.

Reactions to a bovine collagen implant. Clinical and immunologic study in 705 patients.

A small percentage of patients treated with bovine collagen implants have adverse reactions involving both the cellular and humoral types of immune response. We report a clinical follow-up of 705 subjects treated with a new bovine collagen implant, Atelocollagen (Koken Co. Ltd., Tokyo, Japan). Sensitization to the implant was evaluated in all subjects by skin testing, and humoral response was monitored in 166 subjects by measuring the level of circulating antibodies directed against bovine collagen. Twenty-seven patients (3.8%) exhibited a positive response to a skin test, and of the remaining 656 patients, an adverse reaction to the implant developed in 2.3%. We found a strong correlation between the presence of antibodies to collagen and a positive response to skin testing (92%) or an adverse reaction (100%). In the case of a borderline clinical response to bovine collagen implantation, anticollagen serologic tests appeared to be a useful tool for the identification of clinically reactive patients.

Studies on type II collagen induced arthritis in rats: an experimental model of peripheral and axial ossifying enthesopathy.

It was suggested that type II collagen induced arthritis in rats may be considered an experimental model for rheumatoid arthritis (RA) because of clinical, histological, and immunological similarities. However, some features separate it from RA. We studied 40 inbred female Wistar Furth rats. Two weeks after immunization with native human type II collagen, they had polyarthritis which progressed to ankylosis associated with ossifying enthesopathy and periosteal new bone formation. Inflammatory nodules of the tail appeared after 2 months, with radiological and histopathological aspects of multistage spondylodiscitis. Our findings suggest that collagen induced arthritis may be a relevant model of peripheral and axial ossifying enthesopathy.

Antibodies to types I, II, IX, and XI collagen in the serum of patients with rheumatic diseases.

Antibodies to native types I, II, IX, and XI collagen were measured, using a 125I-solid-phase radioimmunoassay, in serum from 104 patients with rheumatic diseases (rheumatoid arthritis, osteoporosis, Paget's disease, or osteoarthritis). In all disease groups, antibodies to type II collagen occurred with greater frequency than antibodies to type I collagen (11-35% versus 5-23%). Antibodies to type XI collagen were the most frequent: They were present in approximately 50% of the patients in the rheumatoid arthritis, Paget's disease, and osteoporosis groups. Antibodies to type IX collagen were found at a high frequency in the rheumatoid arthritis group only (44%). Analysis of the clinical data suggested that the presence of antibodies to collagen was associated with disease that was less severe or of shorter duration.