{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:35:24Z","timestamp":1760142924243,"version":"build-2065373602"},"reference-count":119,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Superantigens, i.e., staphylococcal enterotoxins and toxic shock syndrome toxin-1, interact with T cells in a different manner in comparison to conventional antigens. In fact, they activate a larger contingent of T lymphocytes, binding outside the peptide-binding groove of the major histocompatibility complex class II. Involvement of many T cells by superantigens leads to a massive release of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-2, IL-6, tumor necrosis factor-alpha and interferon-gamma. Such a storm of mediators has been shown to account for tissue damage, multiorgan failure and shock. Besides conventional drugs and biotherapeutics, experiments with natural and biological products have been undertaken to attenuate the toxic effects exerted by superantigens. In this review, emphasis will be placed on polyphenols, probiotics, beta-glucans and antimicrobial peptides. In fact, these substances share a common functional denominator, since they skew the immune response toward an anti-inflammatory profile, thus mitigating the cytokine wave evoked by superantigens. However, clinical applications of these products are still scarce, and more trials are needed to validate their usefulness in humans.<\/jats:p>","DOI":"10.3390\/pathophysiology31010002","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T04:38:51Z","timestamp":1704775131000},"page":"18-31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Current Views about the Inflammatory Damage Triggered by Bacterial Superantigens and Experimental Attempts to Neutralize Superantigen-Mediated Toxic Effects with Natural and Biological Products"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-8124","authenticated-orcid":false,"given":"Luigi","family":"Santacroce","sequence":"first","affiliation":[{"name":"Section of Microbiology and Virology, Interdisciplinary Department of Medicine, School of Medicine, University of Bari \u2018Aldo Moro\u2019, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6661-8116","authenticated-orcid":false,"given":"Skender","family":"Topi","sequence":"additional","affiliation":[{"name":"Department of Clinical Disciplines, University \u2018Alexander Xhuvani\u2019 of Elbasan, 3001 Elbasan, Albania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-7483","authenticated-orcid":false,"given":"Ioannis Alexandros","family":"Charitos","sequence":"additional","affiliation":[{"name":"Division of Pneumology and Respiratory Rehabilitation, Maugeri Clinical Scientific Research Institutes (IRCCS) of Pavia\u2014Scientific Institute of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Lovero","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit, AOU Policlinico Consorziale di Bari-Ospedale Giovanni XXIII, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Luperto","sequence":"additional","affiliation":[{"name":"Brindisi Local Health Agency, 72100 Brindisi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-7377","authenticated-orcid":false,"given":"Raffaele","family":"Palmirotta","sequence":"additional","affiliation":[{"name":"Section of Microbiology and Virology, Interdisciplinary Department of Medicine, School of Medicine, University of Bari \u2018Aldo Moro\u2019, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Jirillo","sequence":"additional","affiliation":[{"name":"Section of Microbiology and Virology, Interdisciplinary Department of Medicine, School of Medicine, University of Bari \u2018Aldo Moro\u2019, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1249098","DOI":"10.3389\/fimmu.2023.1249098","article-title":"Role of toll-like receptors and nod-like receptors in acute lung infection","volume":"14","author":"Le","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101812","DOI":"10.1016\/j.smim.2023.101812","article-title":"Epithelial inflammasomes, gasdermins, and mucosal inflammation\u2014Lessons from Salmonella and Shigella infected mice","volume":"70","author":"Fattinger","year":"2023","journal-title":"Semin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1038\/s12276-023-01088-9","article-title":"Unconventional immune cells in the gut mucosal barrier: Regulation by symbiotic microbiota","volume":"55","author":"Yoo","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Santacroce, L., Imbimbo, C., Ballini, A., Crocetto, F., Scacco, S., Cantore, S., Di Zazzo, E., Colella, M., and Jirillo, E. (2022). Testicular Immunity and Its Connection with the Microbiota. Physiological and Clinical Implications in the Light of Personalized Medicine. J. Pers. Med., 12.","DOI":"10.3390\/jpm12081335"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1146\/annurev-immunol-093019-112809","article-title":"Tissue-Resident Immune Cells in Humans","volume":"40","author":"Gray","year":"2022","journal-title":"Annu. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.jaci.2023.06.014","article-title":"Innate (learned) memory","volume":"152","author":"Al","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/s41419-022-05155-3","article-title":"Chromatin-Associated Molecular Patterns (CAMPs) in sepsis","volume":"13","author":"Nofi","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"843","DOI":"10.4049\/jimmunol.2200173","article-title":"Casting a Wide NET","volume":"209","author":"Kaplan","year":"2022","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"aaf1098","DOI":"10.1126\/science.aaf1098","article-title":"Trained immunity: A program of innate immune memory in health and disease","volume":"352","author":"Netea","year":"2016","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nature01441","article-title":"CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes","volume":"421","author":"Janssen","year":"2003","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1126\/science.1082305","article-title":"Requirement for CD4 T cell help in generating functional CD8 T cell memory","volume":"300","author":"Shedlock","year":"2003","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"855","DOI":"10.4049\/jimmunol.2200037","article-title":"Med1 Controls Effector CD8+ T Cell Differentiation and Survival through C\/EBP\u03b2-Mediated Transcriptional Control of T-bet","volume":"209","author":"Jiao","year":"2022","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nri3803","article-title":"A brief history of T cell help to B cells","volume":"15","author":"Crotty","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41577-018-0007-5","article-title":"Understanding the drivers of MHC restriction of T cell receptors","volume":"18","author":"Gras","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nri3307","article-title":"Transcriptional control of effector and memory CD8+ T cell differentiation","volume":"12","author":"Kaech","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nri.2015.10","article-title":"The multifaceted role of CD4(+) T cells in CD8(+) T cell memory","volume":"16","author":"Laidlaw","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.immuni.2008.11.002","article-title":"Homeostasis of naive and memory T cells","volume":"29","author":"Surh","year":"2008","journal-title":"Immunity."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Noli Truant, S., Redolfi, D.M., Sarratea, M.B., Malchiodi, E.L., and Fern\u00e1ndez, M.M. (2022). Superantigens, a Paradox of the Immune Response. Toxins, 14.","DOI":"10.3390\/toxins14110800"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"eade7168","DOI":"10.1126\/sciimmunol.ade7168","article-title":"Gutsy memory T cells stand their ground against pathogens","volume":"7","author":"Jensen","year":"2022","journal-title":"Sci. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev.immunol.17.1.435","article-title":"The structural basis of T cell activation by superantigens","volume":"17","author":"Li","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kolla, H.B., Tirumalasetty, C., Sreerama, K., and Ayyagari, V.S. (2021). An immunoinformatics approach for the design of a multi-epitope vaccine targeting super antigen TSST-1 of Staphylococcus aureus. J. Genet. Eng. Biotechnol., 19.","DOI":"10.1186\/s43141-021-00160-z"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1871530321666210127141945","article-title":"An Alternative \u201cTrojan Horse\u201d Hypothesis for COVID-19: Immune Deficiency of IL-10 and SARS-CoV-2 Biology","volume":"22","author":"Balzanelli","year":"2022","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1084\/jem.167.3.752","article-title":"Toxic shock syndrome toxin 1 as an inducer of human tumor necrosis factors and gamma interferon","volume":"167","author":"Jupin","year":"1988","journal-title":"J. Exp. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.4049\/jimmunol.161.3.1204","article-title":"Induction of acute inflammation in vivo by staphylococcal superantigens. II. Critical role for chemokines, ICAM-1, and TNF-alpha","volume":"161","author":"Tessier","year":"1998","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/jlb.56.4.458","article-title":"Costimulatory receptors for the superantigen staphylococcal enterotoxin B on human vascular endothelial cells and T cells","volume":"56","author":"Krakauer","year":"1994","journal-title":"J. Leukoc. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Magrone, T., Magrone, M., Russo, M.A., and Jirillo, E. (2019). Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies. Antioxidants, 9.","DOI":"10.20944\/preprints201912.0030.v1"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"940454","DOI":"10.3389\/fmed.2022.940454","article-title":"Probiotics and probiotic-based vaccines: A novel approach for improving vaccine efficacy","volume":"9","author":"Kazemifard","year":"2022","journal-title":"Front. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.ijbiomac.2022.08.173","article-title":"Research progress on natural \u03b2-glucan in intestinal diseases","volume":"219","author":"Han","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.ijantimicag.2004.09.005","article-title":"Antimicrobial peptides: Premises and promises","volume":"24","author":"Reddy","year":"2004","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.2174\/1381612824666180327155230","article-title":"Antimicrobial peptides in human disease: Therapeutic approaches. Second of two parts","volume":"24","author":"Magrone","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eaat0687","DOI":"10.1126\/sciimmunol.aat0687","article-title":"CD4+ T cell-mediated HLA class II cross-restriction in HIV controllers","volume":"3","author":"Galperin","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/s41590-019-0358-5","article-title":"\u03b3\u03b4 TCR ligands: The quest to solve a 500-million-year-old mystery [published correction appears","volume":"20","author":"Willcox","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"938","DOI":"10.4049\/jimmunol.2001441","article-title":"The RAG1 Ubiquitin Ligase Domain Stimulates Recombination of TCR\u03b2 and TCR\u03b1 Genes and Influences Development of \u03b1\u03b2 T Cell Lineages","volume":"209","author":"Burn","year":"2022","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.immuni.2016.09.015","article-title":"Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion","volume":"45","author":"Ranasinghe","year":"2016","journal-title":"Immunity"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/eji.1830190211","article-title":"Two classes of CD1 genes","volume":"19","author":"Calabi","year":"1989","journal-title":"Eur. J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1126\/science.286.5441.958","article-title":"A direct estimate of the human alphabeta T cell receptor diversity","volume":"286","author":"Arstila","year":"1999","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tian, L., Zhou, W., Wu, X., Hu, Z., Qiu, L., Zhang, H., Chen, X., Zhang, S., and Lu, Z. (2022). CTLs: Killers of intracellular bacteria. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.967679"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.4049\/jimmunol.1102661","article-title":"The role of naive T cell precursor frequency and recruitment in dictating immune response magnitude","volume":"188","author":"Jenkins","year":"2012","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1356540","DOI":"10.1155\/2019\/1356540","article-title":"Intracellular Pathogens: Host Immunity and Microbial Persistence Strategies","volume":"2019","author":"Thakur","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.chom.2014.04.006","article-title":"T cells kill bacteria captured by transinfection from dendritic cells and confer protection in mice","volume":"15","author":"Feo","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"886","DOI":"10.4049\/jimmunol.2200026","article-title":"The Transcription Factor Zfp335 Promotes Differentiation and Persistence of Memory CD8+ T Cells by Regulating TCF-1","volume":"209","author":"Liu","year":"2022","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1206299","DOI":"10.3389\/fimmu.2023.1206299","article-title":"The intestinal \u03b3\u03b4 T cells: Functions in the gut and in the distant organs","volume":"14","author":"Li","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41590-017-0027-5","article-title":"Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses","volume":"19","author":"Park","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cellimm.2015.04.008","article-title":"Human gamma delta T cells: Evolution and ligand recognition","volume":"296","author":"Adams","year":"2015","journal-title":"Cell Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.3389\/fimmu.2018.02636","article-title":"Tissue Adaptations of Memory and Tissue-Resident Gamma Delta T Cells","volume":"9","author":"Khairallah","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1002\/j.1460-2075.1995.tb07300.x","article-title":"Characterization of two distinct MHC class II binding sites in the superantigen staphylococcal enterotoxin A","volume":"14","author":"Dohlsten","year":"1995","journal-title":"EMBO J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1084\/jem.182.3.711","article-title":"Staphylococcal enterotoxin A has two cooperative binding sites on major histocompatibility complex class II","volume":"182","author":"Hudson","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/nsb0795-554","article-title":"Staphylococcal enterotoxins A and B share a common structural motif for binding class II major histocompatibility complex molecules","volume":"2","author":"Ulrich","year":"1995","journal-title":"Nat. Struct. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.1182\/blood-2004-07-2523","article-title":"Superantigen recognition by HLA class II on monocytes up-regulates toll-like receptor 4 and enhances proinflammatory responses to endotoxin","volume":"105","author":"Hopkins","year":"2005","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5008","DOI":"10.4049\/jimmunol.170.10.5008","article-title":"Superantigen-induced regulatory T cells display different suppressive functions in the presence or absence of natural CD4+CD25+ regulatory T cells in vivo","volume":"170","author":"Cederbom","year":"2003","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/j.1365-2672.2010.04927.x","article-title":"Superantigenic activity of toxic shock syndrome toxin-1 is resistant to heating and digestive enzymes","volume":"110","author":"Li","year":"2011","journal-title":"J. Appl. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1146\/annurev.immunol.021908.132706","article-title":"T cell activation","volume":"27","author":"Koretzky","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1146\/annurev.iy.11.040193.001203","article-title":"The role of the CD28 receptor during T cell responses to antigen","volume":"11","author":"Linsley","year":"1993","journal-title":"Annu. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3389\/fimmu.2012.00273","article-title":"PKC-theta-mediated signal delivery from the TCR\/CD28 surface receptors","volume":"3","author":"Isakov","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"759","DOI":"10.4161\/viru.23905","article-title":"The staphylococcal enterotoxin (SE) family: SEB and siblings","volume":"4","author":"Krakauer","year":"2013","journal-title":"Virulence"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3389\/fimmu.2013.00384","article-title":"Regulation of immune system cell functions by protein kinase C","volume":"4","author":"Isakov","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Santacroce, L., Colella, M., Charitos, I.A., Di Domenico, M., Palmirotta, R., and Jirillo, E. (2023). Microbial and Host Metabolites at the Backstage of Fever: Current Knowledge about the Co-Ordinate Action of Receptors and Molecules Underlying Pathophysiology and Clinical Implications. Metabolites, 13.","DOI":"10.3390\/metabo13030461"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Peng, L., Jiang, J., Chen, T., Xu, D., Hou, F., Huang, Q., Peng, Y., Ye, C., Hu, D.L., and Fang, R. (2021). Toxic Shock Syndrome Toxin 1 Induces Immune Response via the Activation of NLRP3 Inflammasome. Toxins, 13.","DOI":"10.3390\/toxins13010068"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Krakauer, T. (2019). Staphylococcal Superantigens: Pyrogenic Toxins Induce Toxic Shock. Toxins, 11.","DOI":"10.3390\/toxins11030178"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.rvsc.2008.07.020","article-title":"Central roles for IL-2 and MCP-1 following intranasal exposure to SEB: A new mouse model","volume":"86","author":"Huzella","year":"2009","journal-title":"Res. Vet. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3588","DOI":"10.1128\/IAI.02110-14","article-title":"Superantigens subvert the neutrophil response to promote abscess formation and enhance Staphylococcus aureus survival in vivo","volume":"82","author":"Xu","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.4049\/jimmunol.158.4.1862","article-title":"Induction of acute inflammatory lung injury by staphylococcal enterotoxin B","volume":"158","author":"Neumann","year":"1997","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"470","DOI":"10.2174\/1871530322666220629101357","article-title":"Subversion of the Oral Microbiota and Induction of Immune-Mediated Systemic Inflammation with Special Reference to Periodontitis. Current Knowledge and Perspectives","volume":"23","author":"Santacroce","year":"2023","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1159\/000100858","article-title":"Protein Fv: An endogenous immunoglobulin superantigen and superallergen","volume":"93","author":"Bouvet","year":"2007","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1159\/000100896","article-title":"Role of superallergens in allergic disorders","volume":"93","author":"Marone","year":"2007","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1111\/all.13175","article-title":"Staphylococcus aureus enterotoxin sensitization is associated with allergic poly-sensitization and allergic multimorbidity in adolescents","volume":"72","author":"Klingenberg","year":"2017","journal-title":"Allergy"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1096\/fj.09-151340","article-title":"JNK1 and IKKbeta: Molecular links between obesity and metabolic dysfunction","volume":"24","author":"Solinas","year":"2010","journal-title":"FASEB J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.4049\/jimmunol.1302549","article-title":"Cutting edge: Endoplasmic reticulum stress licenses macrophages to produce mature IL-1\u03b2 in response to TLR4 stimulation through a caspase-8- and TRIF-dependent pathway","volume":"192","author":"Shenderov","year":"2014","journal-title":"J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Santacroce, L., Palmirotta, R., Bottalico, L., Charitos, I.A., Colella, M., Topi, S., and Jirillo, E. (2023). Crosstalk between the Resident Microbiota and the Immune Cells Regulates Female Genital Tract Health. Life, 13.","DOI":"10.3390\/life13071531"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1089\/ars.2015.6407","article-title":"The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases","volume":"23","author":"Nakahira","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ejphar.2013.08.050","article-title":"Mechanisms of staphylococcal enterotoxin-induced emesis","volume":"722","author":"Hu","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_73","first-page":"1911","article-title":"Evaluation of procalcitonin, Vitamin D and C-reactive protein levels in septic patients with positive emocoltures. Our preliminary experience","volume":"32","author":"Lovero","year":"2016","journal-title":"Acta Med. Mediterr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1128\/CVI.00329-10","article-title":"Characterization of infecting strains and superantigen-neutralizing antibodies in Staphylococcus aureus bacteremia","volume":"18","author":"Grumann","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1136\/archdischild-2018-316322","article-title":"New perspectives on Kawasaki disease","volume":"104","author":"Burns","year":"2019","journal-title":"Arch. Dis. Child."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3390\/pathophysiology29030041","article-title":"Biomolecular Mechanisms of Autoimmune Diseases and Their Relationship with the Resident Microbiota: Friend or Foe?","volume":"29","author":"Topi","year":"2022","journal-title":"Pathophysiology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1111\/febs.15512","article-title":"Kawasaki syndrome: Role of superantigens revisited","volume":"288","author":"Leung","year":"2021","journal-title":"FEBS J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"494","DOI":"10.3390\/idr13020048","article-title":"Cardiac Involvement in COVID-19 Patients: A Contemporary Review","volume":"13","author":"Carretta","year":"2021","journal-title":"Infect. Dis. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1056\/NEJM200503103521028","article-title":"Immunosuppressive drugs for kidney transplantation [published correction appears","volume":"352","author":"Halloran","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/019262301316905336","article-title":"Cellular and cytokine responses in the circulation and tissue reactions in the lung of rhesus monkeys (Macaca mulatta) pretreated with cyclosporin A and challenged with staphylococcal enterotoxin B","volume":"29","author":"Komisar","year":"2001","journal-title":"Toxicol. Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.micinf.2012.01.001","article-title":"The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia","volume":"14","author":"Tilahun","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1182\/blood-2004-10-3932","article-title":"Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells","volume":"105","author":"Battaglia","year":"2005","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1086\/381979","article-title":"Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: Implications for therapy of toxic shock syndrome","volume":"38","author":"Darenberg","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1128\/IAI.01121-09","article-title":"Potent neutralization of staphylococcal enterotoxin B by synergistic action of chimeric antibodies","volume":"78","author":"Tilahun","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Larkin, J., Hatswell, A.J., Nathan, P., Lebmeier, M., and Lee, D. (2015). The Predicted Impact of Ipilimumab Usage on Survival in Previously Treated Advanced or Metastatic Melanoma in the UK. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145524"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Varshney, A.K., Wang, X., Cook, E., Dutta, K., Scharff, M.D., Goger, M.J., and Fries, B.C. (2014). Generation, characterization, and epitope mapping of neutralizing and protective monoclonal antibodies against staphylococcal enterotoxin B-induced lethal shock. J. Biol. Chem., 289.","DOI":"10.1074\/jbc.A110.212407"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.4049\/jimmunol.1601525","article-title":"Interference of the T Cell and Antigen-Presenting Cell Costimulatory Pathway Using CTLA4-Ig (Abatacept) Prevents Staphylococcal Enterotoxin B Pathology","volume":"198","author":"Whitfield","year":"2017","journal-title":"J. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.2174\/1871530320999200831224302","article-title":"Taking Advantage of Plant Defense Mechanisms to Promote Human Health. The Plant Immune System. First of Two Parts","volume":"21","author":"Magrone","year":"2021","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.2174\/1381612824666180403123736","article-title":"Antimicrobial Peptides: Phylogenic Sources and Biological Activities. First of Two Parts","volume":"24","author":"Magrone","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Nagy-Bota, M.C., Man, A., Santacroce, L., Brinzaniuc, K., Pap, Z., Pacurar, M., Pribac, M., Ciurea, C.N., Pintea-Simon, I.A., and Kovacs, M. (2021). Essential Oils as Alternatives for Root-Canal Treatment and Infection Control against Enterococcus faecalis\u2014A Preliminary Study. Appl. Sci., 11.","DOI":"10.3390\/app11041422"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2174\/138161212798919011","article-title":"Fermented grape marc (FGM): Immunomodulating properties and its potential exploitation in the treatment of neurodegenerative diseases","volume":"18","author":"Marzulli","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Fujiki, T., Shinozaki, R., Udono, M., and Katakura, Y. (2022). Identification and Functional Evaluation of Polyphenols That Induce Regulatory T Cells. Nutrients, 14.","DOI":"10.3390\/nu14142862"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.1021\/jf904021b","article-title":"Inhibition of biological activity of staphylococcal enterotoxin A (SEA) by apple juice and apple polyphenols","volume":"58","author":"Rasooly","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cellimm.2005.08.030","article-title":"Immune cell activation and subsequent epithelial dysfunction by Staphylococcus enterotoxin B is attenuated by the green tea polyphenol (-)-epigallocatechin gallate","volume":"237","author":"Watson","year":"2005","journal-title":"Cell Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"105548","DOI":"10.1016\/j.phrs.2021.105548","article-title":"Resveratrol-mediated attenuation of superantigen-driven acute respiratory distress syndrome is mediated by microbiota in the lungs and gut","volume":"167","author":"Alghetaa","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s10020-023-00717-3","article-title":"HMGB1 and Toll-like receptors: Potential therapeutic targets in autoimmune diseases","volume":"29","author":"Ren","year":"2023","journal-title":"Mol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1159\/000533602","article-title":"Mitochondrial Damage-Associated Molecular Patterns and Metabolism in the Regulation of Innate Immunity","volume":"15","author":"Lyu","year":"2023","journal-title":"J. Innate Immun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"122027","DOI":"10.1016\/j.lfs.2023.122027","article-title":"Protective effect of \u03b2-glucan on Poly(I:C)-induced acute lung injury\/inflammation: Therapeutic implications of viral infections in the respiratory system","volume":"330","author":"Tirunavalli","year":"2023","journal-title":"Life Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0092-8674(02)01201-1","article-title":"Pattern recognition receptors: Doubling up for the innate immune response","volume":"111","author":"Gordon","year":"2002","journal-title":"Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1006\/bbrc.1998.9175","article-title":"Ligand binding to the (1 --> 3)-beta-D-glucan receptor stimulates NFkappaB activation, but not apoptosis in U937 cells","volume":"249","author":"Battle","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1046\/j.1365-2567.1996.d01-784.x","article-title":"Cytokine production of neutrophils is limited to interleukin-8","volume":"89","author":"Altstaedt","year":"1996","journal-title":"Immunology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1067\/msy.1999.99058","article-title":"Inhibiting early activation of tissue nuclear factor-kappa B and nuclear factor interleukin 6 with (1-->3)-beta-D-glucan increases long-term survival in polymicrobial sepsis","volume":"126","author":"Williams","year":"1999","journal-title":"Surgery"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"449","DOI":"10.4049\/jimmunol.172.1.449","article-title":"Modulation of the phosphoinositide 3-kinase pathway alters innate resistance to polymicrobial sepsis","volume":"172","author":"Williams","year":"2004","journal-title":"J. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Luhm, J., Langenkamp, U., Hensel, J., Frohn, C., Brand, J.M., Hennig, H., Rink, L., Koritke, P., Wittkopf, N., and Williams, D.L. (2006). Beta-(1-->3)-D-glucan modulates DNA binding of nuclear factors kappaB, AT and IL-6 leading to an anti-inflammatory shift of the IL-1beta\/IL-1 receptor antagonist ratio. BMC Immunol., 7.","DOI":"10.1186\/1471-2172-7-5"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Latif, A., Shehzad, A., Niazi, S., Zahid, A., Ashraf, W., Iqbal, M.W., Rehman, A., Riaz, T., Aadil, R.M., and Khan, I.M. (2023). Probiotics: Mechanism of action, health benefits and their application in food industries. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1216674"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1128\/IAI.67.1.244-252.1999","article-title":"Modulation of endotoxin- and enterotoxin-induced cytokine release by in vivo treatment with beta-(1,6)-branched beta-(1,3)-glucan","volume":"67","author":"Soltys","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"992787","DOI":"10.3389\/fimmu.2022.992787","article-title":"Discovery and characterization of SARS-CoV-2 reactive and neutralizing antibodies from humanized CAMouseHG mice through rapid hybridoma screening and high-throughput single-cell V(D)J sequencing","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Arrigoni, R., Ballini, A., Topi, S., Bottalico, L., Jirillo, E., and Santacroce, L. (2022). Antibiotic Resistance to Mycobacterium tuberculosis and Potential Use of Natural and Biological Products as Alternative Anti-Mycobacterial Agents. Antibiotics, 11.","DOI":"10.3390\/antibiotics11101431"},{"key":"ref_109","first-page":"892971","article-title":"Importance of IL-10 modulation by probiotic microorganisms in gastrointestinal inflammatory diseases","volume":"2011","author":"Azevedo","year":"2011","journal-title":"ISRN Gastroenterol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.3168\/jds.2013-7459","article-title":"Effect of cell-surface components and metabolites of lactic acid bacteria and probiotic organisms on cytokine production and induction of CD25 expression in human peripheral mononuclear cells","volume":"97","author":"Ashraf","year":"2014","journal-title":"J. Dairy Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.3748\/wjg.v29.i28.4368","article-title":"Microbiota revolution: How gut microbes regulate our lives","volume":"29","author":"Colella","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Haileselassie, Y., Johansson, M.A., Zimmer, C.L., Bj\u00f6rkander, S., Petursdottir, D.H., Dicksved, J., Petersson, M., Persson, J.O., Fernandez, C., and Roos, S. (2013). Lactobacilli regulate Staphylococcus aureus 161:2-induced pro-inflammatory T-cell responses in vitro. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077893"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3389\/fimmu.2016.00273","article-title":"Probiotic Lactobacilli Modulate Staphylococcus aureus-Induced Activation of Conventional and Unconventional T cells and NK Cells","volume":"7","author":"Johansson","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Ballini, A., Charitos, I.A., Cantore, S., Topi, S., Bottalico, L., and Santacroce, L. (2023). About Functional Foods: The Probiotics and Prebiotics State of Art. Antibiotics, 12.","DOI":"10.3390\/antibiotics12040635"},{"key":"ref_115","first-page":"457","article-title":"Helicobacter pylori infection and gastric MALTomas: An up-to-date and therapy highlight","volume":"159","author":"Santacroce","year":"2008","journal-title":"Clin. Ter."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Merriman, J.A., Nemeth, K.A., and Schlievert, P.M. (2014). Novel antimicrobial peptides that inhibit gram positive bacterial exotoxin synthesis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095661"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"19481","DOI":"10.18632\/oncotarget.24603","article-title":"Interleukin-26 (IL-26) is a novel anti-microbial peptide produced by T cells in response to staphylococcal enterotoxin","volume":"9","author":"Woetmann","year":"2018","journal-title":"Oncotarget"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e972","DOI":"10.1002\/iid3.972","article-title":"The immunomodulatory effects of lactoferrin and its derived peptides on NF-\u03baB signaling pathway: A systematic review and meta-analysis","volume":"11","author":"Yami","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10534-022-00453-x","article-title":"Lactoferrin: From the structure to the functional orchestration of iron homeostasis","volume":"36","author":"Ianiro","year":"2023","journal-title":"Biometals"}],"container-title":["Pathophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1873-149X\/31\/1\/2\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:42:44Z","timestamp":1760103764000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1873-149X\/31\/1\/2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,9]]},"references-count":119,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["pathophysiology31010002"],"URL":"https:\/\/doi.org\/10.3390\/pathophysiology31010002","relation":{},"ISSN":["1873-149X"],"issn-type":[{"type":"electronic","value":"1873-149X"}],"subject":[],"published":{"date-parts":[[2024,1,9]]}}}