Faculty Profile: Laurent Brossay, PHD, MS

Laurent Brossay
Laurent Brossay, PHD, MS
Charles A. & Helen B. Stuart Associate Professor of Medical Science
Molecular Microbiology & Immunology
Work: +1 401-863-9645
The research in our laboratory is directed at understanding the molecular mechanisms controlling the activation of both NK and NK T cells. These two subsets of cells respond quickly to a stimulus and their activation can determine the outcome of an immune response.

Institutions

Bu

Research Description

(NK) cells provide early innate immune recognition and cytolytic response through granule-mediated killing. Additionally, NK cells secrete direct anti-viral as well as immune regulatory cytokines and chemokines, which can promote non-cytolytic pathogen targeting as well as enhance the cytolytic mechanisms and modulate subsequent immune functions. Their rapid activation has become a hallmark of their potency as innate immune system effectors, positioning NK cells as vital players in viral defense. Furthermore, during the response to infectious agents, changes in receptor expression patterns strongly suggest a critical role for activating and inhibitory receptors in the proper regulation of NK cells. We recently demonstrated that the Killer Lectin-Like Receptor G1 (KLRG1) is induced on NK cells during NK cell activation and that NK cell functions can be inhibited by KLRG1. KLRG1 molecule is a recently described C-type lectin inhibitory receptor expressed on resting NK cells and memory T cells. Determination of the precise role of KLRG1 molecule in regulating NK and T cell functions is actively investigated in the laboratory.

Initiation and propagation of the immune response is the result of a series of coordinated cellular and biochemical interactions that lead to the activation of multiple cell types. It is now clear that an optimal immune response requires a precise and rapid communication between different cell subsets. This phenomenon, referred to as cross-talk, is believed to be an essential component of the immune response that provides necessary inflammatory mediators and cytolytic activity for controlling infections and diseases. An example of an effective cooperation between different cell types has been recently illustrated by the finding that specific activation of CD1 restricted NK T cells can quickly lead to the activation of other subsets of cells such as NK and CD8 T cells. We are currentlypursuing studies focused on elucidating the mechanism of communication between activated NK T cells and NK cells during viral infection. Modulation of the immune function of these cells could have important implications for the generation of an appropriate immune response to pathogens.

Grants and Awards

Pre-doctoral Fellowship (M. Sc.) from CNRS, France, 1987
Exchange France—Quebec Award, 1988
Medical Research Council Fellowship from Canada, 1994-1997
American Association of Immunologist Junior Faculty Travel Award, 2004

Affiliations

Professional Memberships
American Association of Immunologists
The Society for Natural Immunity

Service Activities
2007-2010: Associate Editor Journal of Immunology
2010-Present: Section Editor Journal of Immunology
2011-Present: Associate Editor Frontiers in NK Cell Biology

Study Sections
Ad Hoc Reviewer NIH Special Emphasis, 2001, 2002, 2003 & 2004
Ad Hoc Reviewer NIH Program Project Application, 2003, 2004, 2007 & 2008
Ad Hoc Reviewer NIH Immunity and Host-Defense (IHD), 2008
Ad Hoc Reviewer NIH Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE), 2008
Ad Hoc Reviewer Stage 1 review of Challenge Grant Applications 2009
Member NIH Immunity and Host-Defense (IHD) Study Section, 2009-present

Funded Research

- NIH Grant RO1 AI 46709 (6-10); NK T cell interaction with NK cells during viral infections.
07/01/2007 - 06/30/2012

- NIH Grant RO1 AI 058181; Cadherins, Immune Receptors and their Interactions
08/01/2010 - 07/30/2012

Selected Publications

  • Tessmer M. S., Reilly E. C., and L. Brossay. 2011. Salivary gland NK cells are phenotypically and functionally unique. Plos Pathogens. 7(1):e1001254 (2011)
  • Schlub T. E., J. C. Sun, S. M. Walton, S. H. Robbins, A. K. Pinto, M. W. Munks, A. B. Hill, L. Brossay, A. Oxenius, and M. P. Davenport. 2011. Comparing the kinetics of NK cells, CD4 and CD8 T cells in MCMV infection. J. Immunol. 187: 1385–1392 (2011)
  • Wintermeyer, P. C. W. Cheng, S. Gehring, B. L. Hoffman, M. Holub, L. Brossay, and S. H. Gregory. 2009. Invariant NKT Cells Suppress Cholestatic Liver Injury. Gastroenterology. 136: 1048-1059 (2009)
  • Nguyen, V., L. Cao, J. T. Lin, N. Hung, A. Ritz, K. Yu, R. Jianu, S. P. Ulin, B. J. Raphael, D. H. Laidlaw, L. Brossay, and A. R. Salomon. A new approach for quantitative phosphoproteomic dissection of signaling pathways applied to T cell receptor activation. 2009. Molecular & Cellular Proteomics. 8:2418–2431 (2009)
  • Banh, C., C. Fugere and L. Brossay. Immunoregulatory functions of KLRG1 Cadherin interactions are dependent on forward and reverse signaling. 2009. Blood. 114: 5299-5306 (2009)
  • Pilbeam, K., P. Basse, L. Brossay, N. Vujanovic, R. Gerstein, A. N. Vallejo and L. Borghesi. 2008 The ontogeny and fate of natural killer cells marked by permanent DNA rearrangements. J. Immunol. 180 1432-1441 (2008)
  • Chaix J., M. S. Tessmer, K. Hoebe, N. Fuséri, B. Ryffel, M. Dalod, L. Alexopoulou, B. Beutler, L Brossay, E. Vivier, and T. Walzer. Priming of Natural Killer cells by Interleukin-18. J. Immunol. Cutting Edge 181 1627-1631 (2008)
  • Guia, S. C. Cognet, L. de Beaucoudrey, M. S Tessmer, E. Jouanguy, C. Berger, O. Filipe-Santos, J. Feinberg, Y. Camcioglu, J. Levy, S. Al Jumaah, J. L. Stephan, C. Fieschi, L. Abel, L. Brossay, J. L. Casanova, and E. Vivier. 2008 A role for interleukin-12/-23 in the maturation of human Natural Killer and CD56+ T cells in vivo. Blood, 111: 5008-5016 (2008)
  • Wesley, J., M. S. Tessmer, D. Chaukos, and L. Brossay. 2008. NK cell-like behavior of Vα14i NK T cells during MCMV infection. Plos Pathogens. 4(7):e1000106. (2008)
  • Tessmer, M. S., C. Fugère, F. Stevenaert , O. V. Naidenko, H. G. Chong, G. Leclercq, and L. Brossay. 2007. KLRG1 binds cadherins and preferentially associates with SHIP-1. International. Immunol. 19: 391-400 (2007)
  • Wesley, J., M. S. Tessmer, C. Paget, F. Trottein, and L. Brossay. 2007. A Y-chromosome linked factor impairs NK T development. J. Immunol. 179: 3480-3487 (2007)
  • Lawton, A. P., T. I. Prigozy, L. Brossay, A. Khurana, D. Martin, T. Zhu, J. S. Bonifacino, and M. Kronenberg. 2005. The mouse CD1d cytoplasmic tail mediates CD1d trafficking and antigen presentation by AP-3 dependent and independent mechanisms. J. Immunol. 174: 3179-3189 (2005)
  • Robbins, S. H., M. S. Tessmer, L. Van Kaer, and L. Brossay. 2005. Direct effects of T-bet and MHC class I expression, but not STAT1, on peripheral NK cell maturation. Eur. J. Immunol. 35: 757-765 (2005)
  • Wesley, J. D., S. H Robbins, S. C. Terrizzi, and L. Brossay. 2005. Optimal NK T cell activation of NK cells requires functional IFN-? signaling on antigen presenting cells. J. Immunol. 174: 3864-3868 Cutting Edge Report (2005)
  • Anfossi N., S H. Robbins, S. Ugolini, P. Georgel, K. Hoebe, C. Bouneaud, C. Ronet, A. Kaser, C. B. DiCioccio, E. Tomasello, R. S. Blumberg, B. Beutler, S. Reiner, L. A., O. Lantz, D. H. Raulet, L. Brossay and E. Vivier. 2004. Induction and function of CD8+ T cells expressing Ly49 inhibitory receptors specific for MHC class I molecules. J Immunology, in press (2004)
  • Robbins, S. H., M. S. Tessmer, T. Mikayama, and L. Brossay. 2004. Expansion and Contraction of the NK Cell Compartment in Response to MCMV Infection. J Immunology. 173: 259-266 (2004)
  • Eash S., R. Tavares, E. G. Stopa, S. H. Robbins, L. Brossay, and W. J. Atwood. 2004. Differential Distribution of the JC Virus Receptor-Type Sialic Acid in Normal Human Tissues. American J. of Pathology. 164:419-428 (2004)
  • Tessmer, M.S., S.H., Robbins, and L. Brossay. 2004. Development of murine NK cells and their maturation and activation during viral infection. Recent Res. Devel. Immunol. 6: 61-77 (2004)
  • Rhee R. J., S. Carlton, J. L. Lomas, C. Lane, L. Brossay, W. G. Cioffi, and A. Ayala. Inhibition of CD1d activation suppresses septic mortality: a role for NK-T cells in septic immune dysfunction. J Surg Res. 2003 115:74-81. (2003)
  • Robbins, S. H., S. C. Terrizzi, T. Mikayama, B. C. Sydora, and L. Brossay. 2003. Differential regulation of KLRG1 expression on T cells. J. Immunol. 170: 5876-5885 (2003)
  • Maverakis, E., J. Beech, D. B. Stevens, A. Ametani, L. Brossay, P. van den Elzen, R. Mendoza, Q. Thai, L. H. Macias, D. Ethell, C. W. Campagnoni, A. T. Campagnoni, A. Sette, and E. E. Sercarz. 2003. Autoreactive T cells can be protected from tolerance induction through competition by flanking determinants for access to class II MHC. Proc. Natl. Acad. Sci. U. S. A. 100: 5342-5347 (2003)
  • Wesley J., and L. Brossay. 2003. NK and NK T cells. A two ways cross talk. Archivum Immunologiae et Therapiae Experimentalis. 51: 121-126 (2003)
  • Robbins, S.H., and L. Brossay. 2002. Forum: NK Cell Receptors: Emerging Roles in Host Defense Against Infectious Agents. Microbes and Infection. 4:1523-1530 (2002)
  • Robbins, S. H. K. B. Nguyen, N. Takahashi, T. Mikayama, C. A. Biron and L. Brossay. 2002. Inhibitory Functions of the Killer Lectin-Like Receptor G1 Molecule during the Activation of Murine NK Cells. J. Immunol. 168: 2585-2589. Cutting Edge report. (2002)
  • Biron, C. A., and L. Brossay. 2001. NK cells and NKT cells in innate defense against viral infections. Current Opinion in Immunology 13:458-464. (2001)
  • Prigozy, T., O. Naidenko, P. Qasba, D. Elewaut, L. Brossay, T. Natori, Y. Koezuka, A. Kulkarni and M. Kronenberg. 2001. Processing of carbohydrates is required for glycolipid antigen presentation by CD1d molecules. Science 291: 664-667. (2001)
  • Kamada, N., H. Iijima, K. Kimura, M. Harada, E. Shimizu, S. Motohashi, T. Kawano, H. Shinkai, T. Nakayama, T. Sakai, L. Brossay, Kronenberg M, and Taniguchi M. 2001. Crucial amino acid residues of mouse CD1d for glycolipid ligand presentation to V?14 NKT cells. International Immunol. 13: 853-861 (2001)
  • Burdin, N., L. Brossay, M. Degano, H. Iijima, M. Gui, I. A. Wilson, and M. Kronenberg. 2000. Structural requirements for antigen presentation by mouse CD1. Proc. Natl. Acad. Sci. U. S. A. 97: 10156-10161. (2000)
  • Elewaut, D., L. Brossay, S. M. Santee, O. V. Naidenko, N. Burdin, H. De Winter, C. F. Ware, H. Cheroutre, and M. Kronenberg. 2000. Membrane lymphotoxin is required for the development of different subpopulations of NK T cells. J. Immunol. 165: 671-679 (2000)