Guest Seminars on Sept.18

Guest Seminar at Institut Pasteur of Shanghai

Time: 14:00-16:00, Sep. 18th, 2007
Venue: Conference Room, 4th floor, Institut Pasteur of Shanghai, 225 South Chongqing Road

Host PI: Vincent Deubel

Seminar 1 

Title: Eradication of large tumors in mice by a tritherapy targeting the innate, adaptive and regulatory components of the immune system
Speaker: Claude Leclerc, Unit of Régulation Immunitaire et Vaccinologie, Institut Pasteur Paris

Seminar 2

Title: Regulatory B cells control neonatal immunity in the context of TLR activation
Speaker: Richard Lo-Man, Unité de Biologie des Régulations Immunitaires, Institut Pasteur Paris

Abstracts and background of speakers

Abstract 1:
Using the TC1 tumor model, an aggressively growing tumor cell line that expresses the HPV16 E6 and E7 proteins, we have previously demonstrated that targeting the HPV E7 antigen to dendritic cells using the adenylate cyclase of Bordetella pertussis (CyaA) is an efficient strategy to induce therapeutic antitumor immune responses (Preville, X. et al. Cancer Res 65, 641-9 (2005)). This therapeutic effect was demonstrated by injection of the vaccine, CyaA-E7, to mice 10 days after the graft of tumor cells. Although tumors were already detectable at the time of treatment by the vaccine, this experimental model clearly does not reflect human situation. It is moreover clear that most of the therapies found efficient in mice are inefficient in cancer patients.

Speaker’s background
1973       Maîtrise de Biochimie, Université Paris VII
1974       Diplôme d’Etudes Approfondies d’Immunologie, Université Paris VII
1974       Diplôme du Cours d’Immunologie Approfondie de l’Institut Pasteur
1981       Thèse de Doctorat d’Etat ès-Sciences (PhD), Université Paris VII : "Etude des mécanismes d’activité d’un immunomodulateur, le muramyl dipeptide (MDP)" 250 publications (Immunity, J. Exp Med, PNAS, Nature Medicine, Nature Review Immunology, Cancer Res, Blood, J. Immunol, J. Biol. Chem, Eur J Immunol, J. Virol...) and 20 patents.

Abstract 2:
The susceptibility to infections and the strong Th2 bias observed in neonates are thought to be due to the immaturity of the dendritic cell (DC) compartment. We have analyzed the functional properties of splenic DC in early life as well as their regulation. Purified neonatal conventional and plasmacytoid DC can produce type I IFNs and inflammatory cytokines following appropriate TLR stimulation. However, in vivo activation of IL-10 producing B cells by TLR agonists leads to the incomplete activation of neonatal DCs that fail to produce sufficient IL-12 to prime a Th1 response in neonates.

This regulatory effect involves CD5+ B cells which are particularly abundant in the first two weeks of life. These regulatory B cells are activated by various TLR agonists and viruses. Consequently, in the absence of B cells, neonatal mice can develop stronger inflammatory responses and become lethally susceptible to TLR induced lethal inflammation, whereas wild-type mice are resistant. Interestingly, this phenomenon is dependent on type I IFNs production by DC through their capacity to enhance IL-10 secretion by TLR-activated B cells. Therefore, type I IFNs help to control neonatal acute inflammation whereas they enhance the inflammatory response to in adult mice.

In conclusion, neonatal CD5+ B cells control innate pDC and cDC functions in vivo for Th1/Th2 polarization and for inflammatory responses with important implications for neonatal inflammation and infection.

Related publications :
Sun, C. M. et al. Blood 102, 585-91. 2003.
Sun, C. M. et al. Immunity 22, 467-77. 2005.
Zhang, X. et al. J. Exp. Med. 204:1107-1118. 2007.

Speaker’s background:
Hired at the Pasteur Institute in 1997, my research work is dedicated to immunology towards vaccinology. I am particularly interested in in vivo studies that lead to a better knowledge on how immune effector functions can be switched on or not and that take into account the complexity of in situ interactions between immune partners. I have been working on CD4 T cell immunodominance, on host-bacteria interaction in the modulation of immune responses, on a glycopeptidic anti-cancer vaccine candidate, and more recently on neonatal immunity.

1989: MSc. in Organic Chemistry, University of Paris VI, France
1991: Diploma in Advanced Studies in Immunology, University of Paris VI France
1995: PhD. In Immunology, University of Paris VI, France
1997-2001: Research Assistant (Pasteur Institute)
2002- present: Researcher (Pasteur Institute)
41 publications (Immunity, J. Exp. Med., Cancer Res, Blood, J. Immunol…) / 3 patents