Immune Regulation and Vaccinology - INSERM U352  


  HEADProf. LECLERC Claude / cleclerc@pasteur.fr
  MEMBERSDr BERRAONDO Pedro / Dr DADAGLIO Gilles / DERIAUD Edith
Dr FAYOLLE Catherine / FONTE BOA NASCIMENTO Juliana / Dr OLIVIER Aurélie
JARON Barbara / Dr LO-MAN Richard / Dr MAJLESSI Laleh / MOURIES Juliette
ZHANG Xiaoming


  Annual Report

The activity of our laboratory is focused on the understanding of the mechanisms that control the activation and regulation of T cell responses and on the development of new strategies of vaccination against tumors and infections.

The adenylate cyclase (CyaA) of Bordetella pertussis: a new vector targeting dendritic cells Based on the capacity of the adenylate cyclase (CyaA) to bind to dendritic cells (DC), we have developed a highly efficient vector capable of targeting a wide range of antigens to antigen presenting cells, leading to strong immune responses. Based on this vector, we have developed a therapeutic vaccine candidate against cervical cancer. Administration of this vaccine with CpG complexed with a cationic lipid and low-dose cyclophosphamide completely overcame tumor-associated immunosuppression and eradicated large, established tumors in mice. We have also established the effectiveness in non-human primates of an anti-HIV-1 vaccine candidate based on the CyaA vector carrying the Tat protein.

Analysis of T cell responses induced by dendritic cell subpopulations. Plasmacytoid DC (pDC) have been recently identified in mouse lymphoid organs. We showed that pDC induced antigen-specific effector/memory T cells after stimulation by heat-inactivated influenza virus. Our recent results also established that pDC capture and cross-present soluble or particulate antigens in vivo following stimulation by TLR7 or TLR9 ligands leading to cross-priming of naive CD8+ T cells. Thus, pDC can play a role in both innate and adaptive anti-viral immunity.

Ontogeny, functions and regulation of neonatal dendritic cells. We are investigating the con-tribution of DC to the high susceptibility to infections and to biased Th2 responses observed in newborns. We found that neonatal DC are fully functional for innate responses and in their capacity to prime Th1 responses. However, following TLR triggering in vivo, a crosstalk between neonatal B cells and DC is engaged leading to restricted proinflammatory and Th1 responses. This regulatory mechanism involves CD5+B cells and is dependent on IL-10, and likely contributes to neonatal susceptibility to infections.

Investigation of mechanisms of anti-mycobacterial immunity. Induction of Th1 responses to mycobacterial antigens is essential in protection against infection with M. tuberculosis. We demonstrated the potential value of the TB10.4 antigen as a vaccine candidate and showed that high frequencies of CD4+ T cells specific to this strong immunogen correlates with protection against M. tuberculosis infection. We also showed that the presentation of mycobacterial antigens and induction of T-cell immunity are independent of the site of intracellular residence inside professional antigen presenting cells. Indeed, infection of macrophages or dendritic cells in vitro with mycobacterial mutants that are unable to escape lysosomal transfer resulted in an identical efficiency of antigen presentation compared to wild type mycobacteria.



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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