9 research outputs found

    Phagocytic and non-phagocytic cells are targeted by Salmonella Typhimurium in chicks independently of the three known invasion factors

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    International audienceSalmonella are among the most important foodborne pathogens and contaminated poultry meat and eggs are the main source of human infection. Asymptomatic Salmonella carrier state in poultry renders the identification of infected poultry farms difficult. In this context, controlling animal infections is of primary importance. In many infectious models, cell and tissue tropism govern disease. It is therefore important to identify the host cells targeted in vivo by a pathogen and the entry routes used by this pathogen to invade the different host cells. Our aim was thus to identify the host-cell types infected in chicks and to determine the role in this process of the three Salmonella invasion factors known today: the type III secretion system T3SS-1 and the two outer membrane proteins Rck and PagN. After intracelomic inoculation of chicks, the fluorescent wildtype S. Typhimurium 14028 strain and its isogenic mutant deleted of the three know invasion factors were detected using flow-cytometry. Cell invasion was confirmed by confocal microscopy. Our results show that phagocytic and non-phagocytic cells, including immune cells, epithelial and endothelial cells, are invaded by both the wild-type and the mutant strain in vivo in the gall bladder, liver, spleen and vessels. In line with these results, mutants defective for the T3SS-1 or the three known invasion factors, better colonized chicks than their wild-type parent strain. All together, these findings provide new insights into the dynamics of Salmonella spread in vivo in chicks at the organ and cellular levels

    Characterization of intestinal macrophages and dendritic cell subsets in neonatal lambs at homeostasis and following Cryptosporidium parvum infection

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    International audienceCryptosporidiosis is a poorly controlled zoonosis caused by an intestinal parasite, Cryptosporidium parvum (Cp), with a high prevalence in livestock (cattle, sheep, goats). Young animals are particularly susceptible to this infection due to the immaturity of their intestinal immune system. In a neonatal mouse model, we previously demonstrated the importance of the innate immunity and in particular of CD11c+CD103+CD11b-conventional dendritic cells (cDC) among mononuclear phagocytes (MP) in controlling the acute phase of Cp infection. During infection, in response to chemokine production by infected epithelial cells, newly recruited cDCs produce IL12 and IFNγ contributing to the elimination of the parasite. According to the well-established mouse cDC classification, this Batf3+DC subpopulation corresponds to the cDC1 subset. The aim of this project was to better characterize intestinal MP subpopulations in neonatal lamb and calf at homeostasis and during Cp infection. As in the mouse model, the parasite invades and multiplies mainly in the ileum of animals. However, a peculiarity of young ruminants is the presence of a large ileal Peyer’s patch (lymphoid tissue) that extends all along the ileum. MP were therefore analyzed in lymphoid and non-lymphoid intestinal tissues of lambs and claves. We performed phenotypic and functional analyses of mononuclear phagocytes by flow cytometry and by transcriptomic methods (FLUIDIGM®) respectively, in the distal jejunum, jejunal and ileal Peyer’s patches. We characterized a population of macrophages and three subpopulations of cDC. We demonstrated that the subset identified as cDC1, according to the current common classification of cDC in different species (human, mouse, pig, sheep and chicken), increases with the age of animal. This might be linked with the decrease in sensitivity to C. parvum observed with the age. We are currently investigating the evolution of cDC1 subset during C. parvum infection

    The adiponectin agonist, AdipoRon, inhibits steroidogenesis and cell proliferation in human luteinized granulosa cells

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    International audienceDuring obesity, excess body weight is not only associated with an increased risk of type 2-diabetes, but also several other pathological processes, such as infertility. Adipose tissue is the largest endocrine organ of the body that produces adipokines, including adiponectin. Adiponectin has been reported to control fertility through the hypothalamic-pituitary-gonadal axis, and folliculogenesis in the ovaries. In this study, we focused on a recent adiponectin-like synthetic agonist called AdipoRon, and its action in human luteinized granulosa cells. We demonstrated that AdipoRon activated the adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPAR) signalling pathways in human luteinized granulosa cells. A 25 mu M AdipoRon stimulation reduced granulosa cell proliferation by inducing cell cycle arrest in G(1), associated with PTEN and p53 pathway activation. In addition, AdipoRon perturbed cell metabolism by decreasing mitochondrial activity and ATP production. In human luteinized granulosa cells, AdipoRon increased phosphodiesterase activity, leading to a drop in cyclic adenosine monophosphate (cAMP) production, ammatase expression and oestrogens secretion. In conclusion, AdipoRon impacted folliculogenesis by altering human luteinized granulosa cell function, via steroid production and cell proliferation. This agonist may have applications for improving ovarian function in metabolic disorders or granulosa cancers
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