Bio

Honors & Awards


  • Best Poster Award, French Association for Cytometry (AFC) (Sept 2012)
  • ACTERIA European Thesis Prize 2013 nomination, French Society for Immunology (Jun 2013)
  • Charles Grupper Prize 2013 Best paper in human Immuno-Dermatology of the year 2013, French Society for Dermatology - LeoPharma Lab (Dec 2013)

Boards, Advisory Committees, Professional Organizations


  • Member, French Society for Immunology (2011 - Present)

Professional Education


  • Master of Science in Engr, Universite Paul Sabatier (2008)
  • Master of Science, Universite Paul Sabatier (2009)
  • Doctor of Philosophy, Universite Paul Sabatier (2012)

Stanford Advisors


Research & Scholarship

Lab Affiliations


Publications

All Publications


  • Melanoma cell lysosome secretory burst neutralizes the CTL-mediated cytotoxicity at the lytic synapse NATURE COMMUNICATIONS Khazen, R., Mueller, S., Gaudenzio, N., Espinosa, E., Puissegur, M., Valitutti, S. 2016; 7

    Abstract

    Human melanoma cells express various tumour antigens that are recognized by CD8(+) cytotoxic T lymphocytes (CTLs) and elicit tumour-specific responses in vivo. However, natural and therapeutically enhanced CTL responses in melanoma patients are of limited efficacy. The mechanisms underlying CTL effector phase failure when facing melanomas are still largely elusive. Here we show that, on conjugation with CTL, human melanoma cells undergo an active late endosome/lysosome trafficking, which is intensified at the lytic synapse and is paralleled by cathepsin-mediated perforin degradation and deficient granzyme B penetration. Abortion of SNAP-23-dependent lysosomal trafficking, pH perturbation or impairment of lysosomal proteolytic activity restores susceptibility to CTL attack. Inside the arsenal of melanoma cell strategies to escape immune surveillance, we identify a self-defence mechanism based on exacerbated lysosome secretion and perforin degradation at the lytic synapse. Interfering with this synaptic self-defence mechanism might be useful in potentiating CTL-mediated therapies in melanoma patients.

    View details for DOI 10.1038/ncomms10823

    View details for Web of Science ID 000371714300001

    View details for PubMedID 26940455

  • IgE antibodies, FceRIa, and IgE-mediated local anaphylaxis can limit snake venom toxicity. journal of allergy and clinical immunology Starkl, P., Marichal, T., Gaudenzio, N., Reber, L. L., Sibilano, R., Tsai, M., Galli, S. J. 2016; 137 (1): 246-257 e11

    Abstract

    Type 2 cytokine-related immune responses associated with development of antigen-specific IgE antibodies can contribute to pathology in patients with allergic diseases and to fatal anaphylaxis. However, recent findings in mice indicate that IgE also can enhance defense against honeybee venom.We tested whether IgE antibodies, IgE-dependent effector mechanisms, and a local anaphylactic reaction to an unrelated antigen can enhance defense against Russell viper venom (RVV) and determined whether such responses can be influenced by immunization protocol or mouse strain.We compared the resistance of RVV-immunized wild-type, IgE-deficient, and Fcer1a-deficient mice after injection of a potentially lethal dose of RVV.A single prior exposure to RVV enhanced the ability of wild-type mice, but not mice lacking IgE or functional FcεRI, to survive challenge with a potentially lethal amount of RVV. Moreover, IgE-dependent local passive cutaneous anaphylaxis in response to challenge with an antigen not naturally present in RVV significantly enhanced resistance to the venom. Finally, we observed different effects on resistance to RVV or honeybee venom in BALB/c versus C57BL/6 mice that had received a second exposure to that venom before challenge with a high dose of that venom.These observations illustrate the potential benefit of IgE-dependent effector mechanisms in acquired host defense against venoms. The extent to which type 2 immune responses against venoms can decrease pathology associated with envenomation seems to be influenced by the type of venom, the frequency of venom exposure, and the genetic background of the host.

    View details for DOI 10.1016/j.jaci.2015.08.005

    View details for PubMedID 26410782

  • IgE antibodies, Fc epsilon RI alpha, and IgE-mediated local anaphylaxis can limit snake venom toxicity JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Starkl, P., Marichal, T., Gaudenzio, N., Reber, L. L., Sibilano, R., Tsai, M., Galli, S. J. 2016; 137 (1): 246-?
  • MPLA shows attenuated pro-inflammatory properties and diminished capacity to activate mast cells in comparison with LPS ALLERGY Schuelke, S., Flaczyk, A., Vogel, L., Gaudenzio, N., Angers, I., Loeschner, B., Wolfheimer, S., Spreitzer, I., Qureshi, S., Tsai, M., Galli, S., Vieths, S., Scheurer, S. 2015; 70 (10): 1259-1268

    Abstract

    Monophosphoryl lipid A (MPLA), a nontoxic TLR4 ligand derived from lipopolysaccharide (LPS), is used clinically as an adjuvant in cancer, hepatitis, and malaria vaccines and in allergen-specific immunotherapy. Nevertheless, its cell-activating effects have not been analyzed in a comprehensive direct comparison including a wide range of different immune cells. Therefore, the objective of this study was the side-by-side comparison of the immune-modulating properties of MPLA and LPS on different immune cells.Immune-activating properties of MPLA and LPS were compared in human monocytes and mast cells (MCs), a mouse endotoxin shock model (ESM), and mouse bone marrow (BM)-derived myeloid dendritic cells (mDCs), T cells (TCs), B cells, and MCs.In a mouse in vivo ESM and a human ex vivo monocyte activation test (MAT), MPLA induced the same cytokine secretion pattern as LPS (ESM: IL-6, IL-12, TNF-α; MAT: IL-1β, IL-6, TNF-α), albeit at lower levels. Mouse mDCs and ex vivo isolated B cells stimulated with MPLA required a higher threshold to induce TRIF-dependent cytokine secretion (IL-1β, IL-6, IL-10, and TNF-α) than did LPS-stimulated cells. In mDC:DO11.10 CD4 TC cocultures, stimulation with MPLA, but not with LPS, resulted in enhanced OVA-specific IL-4 and IL-5 secretion from DO11.10 CD4 TCs. Unexpectedly, in both human and mouse MCs, MPLA, unlike LPS, did not elicit secretion of pro-inflammatory cytokines.Compared to LPS, MPLA induced a qualitatively similar, but less potent pro-inflammatory immune response, but was unable to activate human or mouse MCs.

    View details for DOI 10.1111/all.12675

    View details for Web of Science ID 000362530600009

    View details for PubMedID 26081583

  • Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Gaudenzio, N., Sibilano, R., Starkl, P., Tsai, M., Galli, S. J., Reber, L. L. 2015

    View details for DOI 10.3791/52753

    View details for Web of Science ID 000361535300053

  • Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence NATURE COMMUNICATIONS Joulia, R., Gaudenzio, N., Rodrigues, M., Lopez, J., Blanchard, N., Valitutti, S., Espinosa, E. 2015; 6

    Abstract

    Mast cells are tissue-resident immune cells that play a key role in inflammation and allergy. Here we show that interaction of mast cells with antibody-targeted cells induces the polarized exocytosis of their granules resulting in a sustained exposure of effector enzymes, such as tryptase and chymase, at the cell-cell contact site. This previously unidentified mast cell effector mechanism, which we name the antibody-dependent degranulatory synapse (ADDS), is triggered by both IgE- and IgG-targeted cells. ADDSs take place within an area of cortical actin cytoskeleton clearance in the absence of microtubule organizing centre and Golgi apparatus repositioning towards the stimulating cell. Remarkably, IgG-mediated degranulatory synapses also occur upon contact with opsonized Toxoplasma gondii tachyzoites resulting in tryptase-dependent parasite death. Our results broaden current views of mast cell degranulation by revealing that human mast cells form degranulatory synapses with antibody-targeted cells and pathogens for dedicated secretion and defence.

    View details for DOI 10.1038/ncomms7174

    View details for Web of Science ID 000348833000002

    View details for PubMedID 25629393

  • Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice. Journal of visualized experiments : JoVE Gaudenzio, N., Sibilano, R., Starkl, P., Tsai, M., Galli, S. J., Reber, L. L. 2015

    Abstract

    Mast cells (MCs) are hematopoietic cells which reside in various tissues, and are especially abundant at sites exposed to the external environment, such as skin, airways and gastrointestinal tract. Best known for their detrimental role in IgE-dependent allergic reactions, MCs have also emerged as important players in host defense against venom and invading bacteria and parasites. MC phenotype and function can be influenced by microenvironmental factors that may differ according to anatomic location and/or based on the type or stage of development of immune responses. For this reason, we and others have favored in vivo approaches over in vitro methods to gain insight into MC functions. Here, we describe methods for the generation of mouse bone marrow-derived cultured MCs (BMCMCs), their adoptive transfer into genetically MC-deficient mice, and the analysis of the numbers and distribution of adoptively transferred MCs at different anatomical sites. This method, named the 'mast cell knock-in' approach, has been extensively used over the past 30 years to assess the functions of MCs and MC-derived products in vivo. We discuss the advantages and limitations of this method, in light of alternative approaches that have been developed in recent years.

    View details for DOI 10.3791/52753

    View details for PubMedID 26068439

  • Contribution of Mast Cell-Derived Interleukin-1 beta to Uric Acid Crystal-Induced Acute Arthritis in Mice ARTHRITIS & RHEUMATOLOGY Reber, L. L., Marichal, T., Sokolove, J., Starkl, P., Gaudenzio, N., Iwakura, Y., Karasuyama, H., Schwartz, L. B., Robinson, W. H., Tsai, M., Galli, S. J. 2014; 66 (10): 2881-2891

    View details for DOI 10.1002/art.38747

    View details for Web of Science ID 000342744300026

  • Reply: To PMID 23518141. journal of allergy and clinical immunology Gaudenzio, N., Laurent, C., Valitutti, S., Espinosa, E. 2013; 132 (6): 1458-1459

    View details for DOI 10.1016/j.jaci.2013.09.025

    View details for PubMedID 24184150

  • Human mast cells drive memory CD4(+) T cells toward an inflammatory IL-22(+) phenotype JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Gaudenzio, N., Laurent, C., Valitutti, S., Espinosa, E. 2013; 131 (5): 1400-U240

    Abstract

    Mast cells are key components of the skin microenvironment in psoriasis, yet their functional role in this T-cell-mediated inflammatory disorder remains to be elucidated.To define the impact of T-cell/mast-cell cognate interactions on the cytokines produced by TH cells.We used human primary mast cells and effector/memory CD4(+) T cells for in vitro coculture experiments, and we analyzed TH cells responses by using cytometry. CD4(+) T-cell/mast-cell conjugates in skin lesions from patients with psoriasis were analyzed by using 3-color immunohistochemistry and confocal microscopy.We show that IFN-γ-primed human mast cells formed productive immunologic synapses with antigen-experienced CD4(+) T cells. These interactions promoted the generation of TH22 and IL-22/IFN-γ-producing TH cells from the circulating memory CD4(+) T-cell pool via a TNF-α/IL-6-dependent mechanism. An analysis of human psoriatic skin biopsies showed a rich infiltrate of IL-22(+)CD4(+) T cells frequently found in contact with mast cells. Moreover, most of these mast-cell-conjugated lymphocytes coexpressed IFN-γ, suggesting that IL-22(+)IFN-γ(+) CD4(+) T cells are generated in vivo on interaction with mast cells.Our findings identify human mast cells as functional partners of TH cells, shaping their responses toward IL-22 production.

    View details for DOI 10.1016/j.jaci.2013.01.029

    View details for Web of Science ID 000318912200018

    View details for PubMedID 23518141

  • Cell-cell cooperation at the T helper cell/mast cell immunological synapse BLOOD Gaudenzio, N., Espagnolle, N., Mars, L. T., Liblau, R., Valitutti, S., Espinosa, E. 2009; 114 (24): 4979-4988

    Abstract

    It has been suggested that mast cells might serve, under certain circumstances, as antigen-presenting cells (APCs) for T cells. However, whether cognate interactions between mast cells and class II-restricted CD4(+) T cells actually occur is still an open question. We addressed this question by using peritoneal cell-derived mast cells (PCMCs) and freshly isolated peritoneal mast cells as APC models. Our results show that in vitro treatment of PCMCs with interferon-gamma and interleukin-4 induced surface expression of mature major histocompatibility complex class II molecules and CD86. When interferon-gamma/interleukin-4-primed PCMCs were used as APCs for CD4(+) T cells, they induced activation of effector T cells but not of their naive counterparts as evidenced by CD69 up-regulation, proliferation, and cytokine production. Confocal laser scanning microscopy showed that CD4(+) T cells formed immunological synapses and polarized their secretory machinery toward both antigen-loaded PCMCs and freshly isolated peritoneal mast cells. Finally, on cognate interaction with CD4(+) T cells, mast cells lowered their threshold of activation via FcepsilonRI. Our results show that mast cells can establish cognate interactions with class II-restricted helper T cells, implying that they can actually serve as resident APCs in inflamed tissues.

    View details for DOI 10.1182/blood-2009-02-202648

    View details for Web of Science ID 000272403000014

    View details for PubMedID 19805617