CAROLA AMORMINO

Dottoressa di ricerca

ciclo: XXXVI


relatore: Loretta Tuosto

Titolo della tesi: Characterization of the mechanisms and signalling mediators regulating human toxic shock in response to bacterial superantigens

Staphylococcus aureus is gram-positive bacterium that produces enterotoxins that act as superantigens (SAgs), such as staphylococcal enterotoxin A (SEA) and B (SEB). SAgs are potent toxins that activate T cells to elicit an excessive and harmful inflammatory response known as toxic shock syndrome (TSS). The inflammatory activity of staphylococcal SAgs relies on their ability to bind the T-cell receptor (TCR) and the costimulatory receptor CD28 on T cells as well as the major histocompatibility class II (MHC-II) and B7 molecules on antigen presenting cells (APC). Starting from these evidences, this thesis was aimed to better characterize the role of these molecules on SAg-mediated inflammatory responses. Our data demonstrate that the binding of SEB and SEA to either MHC-II or B7 molecules is dispensable for the activation of inflammatory signals, whereas the binding to the TCR and CD28 is pivotal. Interestingly, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), several weeks after infection, promotes in some children a rare hyperinflammatory disease named multisystem inflammatory syndrome in children (MIS-C) that shares clinical similarity with TSS induced by SAgs. Moreover, recent in silico models suggested the presence in SARS-CoV-2 spike protein of a conserved motif similar in structure to a fragment SEB. However, no experimental data on the superantigenic activity of SARS-CoV-2 spike are avilable. Hence, we also assessed the superatigenic activity of SARS-CoV-2 spike. Our data demonstrate that SARS-CoV-2 spike does not possess an intrinsic superantigenic-like activity. Finally, we highlighted a novel model of T cell activation by staphylococcal SAgs, which by binding the TCR and CD28 in a bivalent way promote a toxic inflammatory response in the absence of APCs.

Produzione scientifica

11573/1681026 - 2023 - Bivalent binding of staphylococcal superantigens to the TCR and CD28 triggers inflammatory signals independently of antigen presenting cells
Kunkl, Martina; Amormino, Carola; Spallotta, Francesco; Caristi, Silvana; Fiorillo, Maria Teresa; Paiardini, Alessandro; Kaempfer, Raymond; Tuosto, Loretta - 01a Articolo in rivista
rivista: FRONTIERS IN IMMUNOLOGY (Lausanne : Frontiers Research Foundation, 2010-) pp. - - issn: 1664-3224 - wos: WOS:000988435800001 (0) - scopus: 2-s2.0-85159695596 (0)

11573/1652973 - 2022 - SARS-CoV-2 spike does not possess intrinsic superantigen-like inflammatory activity
Amormino, Carola; Tedeschi, Valentina; Paldino, Giorgia; Arcieri, Stefano; Fiorillo, Maria Teresa; Paiardini, Alessandro; Tuosto, Loretta; Kunkl, Martina - 01a Articolo in rivista
rivista: CELLS (Basel: mdpi-Molecular Diversity Preservation International) pp. - - issn: 2073-4409 - wos: WOS:000846047100001 (7) - scopus: 2-s2.0-85137600259 (8)

11573/1614635 - 2022 - Astrocytes and inflammatory T Helper Cells: a dangerous liaison in Multiple Sclerosis
Kunkl, M.; Amormino, C.; Tedeschi, V.; Fiorillo, M. T.; Tuosto, L. - 01a Articolo in rivista
rivista: FRONTIERS IN IMMUNOLOGY (Lausanne : Frontiers Research Foundation, 2010-) pp. - - issn: 1664-3224 - wos: WOS:000760495000001 (9) - scopus: 2-s2.0-85125110694 (10)

11573/1569930 - 2021 - Binding of Staphylococcal Enterotoxin B (SEB) to B7 Receptors Triggers TCR- and CD28-Mediated Inflammatory Signals in the Absence of MHC Class II Molecules
Kunkl, M.; Amormino, C.; Caristi, S.; Tedeschi, V.; Fiorillo, M. T.; Levy, R.; Popugailo, A.; Kaempfer, R.; Tuosto, L. - 01a Articolo in rivista
rivista: FRONTIERS IN IMMUNOLOGY (Lausanne : Frontiers Research Foundation, 2010-) pp. - - issn: 1664-3224 - wos: WOS:000698830800001 (6) - scopus: 2-s2.0-85114257046 (7)

11573/1660841 - 2021 - Staphylococcal enterotoxin B (SEB) activates TCR- and CD28-mediated inflammatory signals in the absence of MHC class II molecules
Kunkl, M; Amormino, C; Caristi, S; Tedeschi, V; Fiorillo, Mt; Levy, R; Popugailo, A; Kaempfer, R; Tuosto, L - 04d Abstract in atti di convegno
rivista: EUROPEAN JOURNAL OF IMMUNOLOGY (Wiley-VCH Verlag GmBH:PO Box 101161, D 69451 Weinheim Germany:011 49 6201 606147, EMAIL: service@wiley-vch.de, INTERNET: http://www.wiley-vch.de, Fax: 011 49 6201 606328) pp. 204-204 - issn: 0014-2980 - wos: WOS:000753366401092 (1) - scopus: 2-s2.0-85129990724 (1)
congresso: 6th European Congress of Immunology (Virtual meeting)
libro: 6th European Congress of Immunology, 1–4 September 2021, Virtual meeting - ()

11573/1660843 - 2021 - CD28 individual signaling up-regulates IL-22 expression and IL-22-mediated effector functions in human T lymphocytes
Kunkl, M; Amormino, C; Frascolla, S; Sambucci, M; De Bardi, M; Caristi, S; Arcieri, S; Battistini, L; Tuosto, L - 04d Abstract in atti di convegno
rivista: EUROPEAN JOURNAL OF IMMUNOLOGY (Wiley-VCH Verlag GmBH:PO Box 101161, D 69451 Weinheim Germany:011 49 6201 606147, EMAIL: service@wiley-vch.de, INTERNET: http://www.wiley-vch.de, Fax: 011 49 6201 606328) pp. 181-181 - issn: 0014-2980 - wos: WOS:000753366401006 (0) - scopus: 2-s2.0-85129990724 (1)
congresso: 6th European Congress of Immunology (Virtual meeting)
libro: 6th European Congress of Immunology, 1-4 September 2021, Virtual meeting - ()

11573/1456992 - 2020 - CD28 autonomous signaling orchestrates IL-22 expression and IL-22-regulated epithelial barrier functions in human T lymphocytes
Kunkl, M.; Amormino, C.; Frascolla, S.; Sambucci, M.; De Bardi, M.; Caristi, S.; Arcieri, S.; Battistini, L.; Tuosto, L. - 01a Articolo in rivista
rivista: FRONTIERS IN IMMUNOLOGY (Lausanne : Frontiers Research Foundation, 2010-) pp. - - issn: 1664-3224 - wos: WOS:000586847200001 (6) - scopus: 2-s2.0-85094652605 (5)

11573/1383555 - 2020 - T Helper Cells: The Modulators of Inflammation in Multiple Sclerosis
Kunkl, Martina; Frascolla, Simone; Amormino, Carola; Volpe, Elisabetta; Tuosto, Loretta - 01a Articolo in rivista
rivista: CELLS (Basel: mdpi-Molecular Diversity Preservation International) pp. 482- - issn: 2073-4409 - wos: WOS:000521944900223 (104) - scopus: 2-s2.0-85102724076 (111)

11573/1333288 - 2019 - CD28 and associated class 1A P13K regulates the glycolytic metabolic program associated to pro-inflammatory T cell responses in Multiple Sclerosis
Kunkl, M; Sambucci, M; Ruggeri, S; Amormino, C; Caristi, S; Gasperini, C; Battistini, L; Tuosto, L - 04d Abstract in atti di convegno
rivista: EUROPEAN JOURNAL OF IMMUNOLOGY (Wiley-VCH Verlag GmBH:PO Box 101161, D 69451 Weinheim Germany:011 49 6201 606147, EMAIL: service@wiley-vch.de, INTERNET: http://www.wiley-vch.de, Fax: 011 49 6201 606328) pp. 188-189 - issn: 0014-2980 - wos: WOS:000487085200309 (0) - scopus: 2-s2.0-85072562121 (0)
congresso: 2nd Joint Meeting of the German-Society-for-Immunology (DGfl) and the Italian-Society-of-Immunology-Clinical-Immunology-and-Allergology (SIICA) (Munich, GERMANY)
libro: II Joint Meeting of the German Society for Immunology (DGfl) and the Italian Society of Immunology, Clinical Immunology and Allergology (SIICA) 10-13 September, 2019 Munich, Germany - ()

11573/1301270 - 2019 - CD28 Autonomous Signaling Up-Regulates C-Myc Expression and Promotes Glycolysis Enabling Inflammatory T Cell Responses in Multiple Sclerosis
Kunkl, Martina; Sambucci, Manolo; Ruggieri, Serena; Amormino, Carola; Tortorella, Carla; Gasperini, Claudio; Battistini, Luca; Tuosto, Loretta - 01a Articolo in rivista
rivista: CELLS (Basel: mdpi-Molecular Diversity Preservation International) pp. - - issn: 2073-4409 - wos: WOS:000475309200063 (24) - scopus: 2-s2.0-85082198149 (26)

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