Biomedical subjects

Vincent Feuillet

Publications and source records attributed to Vincent Feuillet.

4 recordsLinked to original sources

PubMed2006

Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria.

Toll-like receptors (TLRs) are key components of the immune system that detect microbial infection and trigger antimicrobial host defense responses. TLR5 is a sensor for monomeric flagellin, which is a component of bacterial flagella known to be a virulence factor. In this study we generated TLR5-deficient mice and investigated the role of TLR5 signaling in the detection of flagellin and antibacterial immune responses to Salmonella typhimurium and Pseudomonas aeruginosa. We found that TLR5 is essential for the recognition of bacterial flagellin both in vivo and ex vivo. TLR5 contribution to antibacterial host response to i.p. infection with S. typhimurium or intranasal administration of P. aeruginosa may be masked by TLR4 or other sensing mechanisms. By using radiation bone marrow chimera, we showed that upon i.p. injection of flagellin immune responses are mediated by lymphoid cells, whereas resident cells are required for the initiation of response upon intranasal flagellin administration. These results suggest that flagellin recognition in different organs is mediated by distinct TLR5-expressing cells and provide insights into the cooperation of the TLR5 and TLR4 signaling pathways used by the innate immune system in the recognition of bacterial pathogens.

Animals↗

PubMed2005

Multifocal structure of the T cell - dendritic cell synapse.

The structure of immunological synapses formed between murine naive T cells and mature dendritic cells has been subjected to a quantitative analysis. Immunofluorescence images of synapses formed in the absence of antigen show a diffuse synaptic accumulation of CD3 and LFA-1. In electron microscopy, these antigen-free synapses present a number of tight appositions (cleft size approximately 15 nm), all along the synapse. These tight appositions cover a significantly larger surface fraction of antigen-dependent synapses. In immunofluorescence, antigen-dependent synapses show multiple patches of CD3 and LFA-1 with a variable overlap. A similar distribution is observed for PKCtheta and talin. A concentric organization characteristic of prototypical synapses is rarely observed, even when dendritic cells are paralyzed by cytoskeletal poisons. In T-DC synapses, the interaction surface is composed of several tens of submicronic contact spots, with no large-scale segregation of CD3 and LFA-1. As a comparison, in T-B synapses, a central cluster of CD3 is frequently observed by immunofluorescence, and electron microscopy reveals a central tight apposition. Our data show that it is inappropriate to consider the concentric structure as a "mature synapse" and multifocal structures as immature.

Animals↗

PubMed2005

Multiple survival signals are delivered by dendritic cells to naive CD4+ T cells.

The molecular mechanisms by which dendritic cells (DC) favor naive T cell survival in mice have been examined in co-cultures of DC and naive CD4+ T cells. Naive T cells can survive in the presence of IL-4 or IL-7, but DC-induced T cell survival requires direct cell-cell interactions and does not seem to be mediated by these or other soluble factors. Classical MHC II molecules on DC are not necessary for T cell survival as long as hybrid AalphaEbeta MHC class II molecules are present. In the total absence of MHC II molecules on DC, T cell survival is reduced by half, and CD3zeta phosphorylation fully disappears. These results contrast with the classical view that naive T cell survival is associated with CD3zeta phosphorylation and depends mostly on IL-7 and MHC-TCR interactions. We demonstrate that DC-induced T cell survival is a multi-factorial process that also involves CD28, LFA-1 and another (as yet undefined) surface molecule that requires the activity of src (but not phosphatidylinositol-3-) kinase.

Animals↗

PubMed2002

The distinct capacity of Fyn and Lck to phosphorylate Sam68 in T cells is essentially governed by SH3/SH2-catalytic domain linker interactions.

Sam68 phosphorylation correlates with Fyn but not Lck expression in T cells. This substrate has been used here to explore the possible basis of the specificity of Fyn versus Lck. We show that this specificity is not based on a spatial segregation of the two kinases, since a chimeric Lck molecule containing the membrane anchoring domain of Fyn does not phosphorylate Sam68. Moreover, a Sam68 molecule targeted to the plasma membrane by the farnesylation signal of c-Ha-Ras remains poorly phosphorylated by Lck. In T cells, Fyn appears to be the active Src kinase in rafts, but Sam68 is not expressed in rafts, and its distinct phosphorylation by Fyn and Lck is not affected by raft dispersion. The Fyn/Lck specificity does not reflect a higher kinase activity of Fyn in general, as both Fyn and Lck are similarly recognized by an anti-active Src antibody. Both also strongly phosphorylate another Src substrate in vivo. Mainly, Lck phosphorylates Sam68 when the interaction between the SH3 domain and the SH2-catalytic domain linker is altered in heterologous Src molecules or after mutating key residues in the linker that increase the accessibility of the SH3 domain. Thus, the distinct potential of Fyn and Lck to phosphorylate Sam68 is likely controlled by the interaction of the kinase SH3 domain with the linker and Sam68, possibly on a competitive binding basis.

Adaptor Proteins, Signal Transducing↗