title: CD81 controls immunity to Listeria infection through rac-dependent inhibition of proinflammatory mediator release and activation of cytotoxic T cells.
abstract: Despite recent evidence on the involvement of CD81 in pathogen binding and Ag presentation by dendritic cells (DCs), the molecular mechanism of how CD81 regulates immunity during infection remains to be elucidated. To investigate the role of CD81 in the regulation of defense mechanisms against microbial infections, we have used the Listeria monocytogenes infection model to explore the impact of CD81 deficiency in the innate and adaptive immune response against this pathogenic bacteria. We show that CD81(-/-) mice are less susceptible than wild-type mice to systemic Listeria infection, which correlates with increased numbers of inflammatory monocytes and DCs in CD81(-/-) spleens, the main subsets controlling early bacterial burden. Additionally, our data reveal that CD81 inhibits Rac/STAT-1 activation, leading to a negative regulation of the production of TNF-α and NO by inflammatory DCs and the activation of cytotoxic T cells by splenic CD8α(+) DCs. In conclusion, this study demonstrates that CD81-Rac interaction exerts an important regulatory role on the innate and adaptive immunity against bacterial infection and suggests a role for CD81 in the development of novel therapeutic targets during infectious diseases.
authors.affiliation: Departamento de Biología Vascular e Inflamación, Fundación Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; gmartinez@cnic.es.
authors.forename: Gloria
authors.initials: G
authors.lastname: Martínez del Hoyo
authors.affiliation: Departamento de Biología Vascular e Inflamación, Fundación Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain;
authors.forename: Marta
authors.initials: M
authors.lastname: Ramírez-Huesca
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94035;
authors.forename: Shoshana
authors.initials: S
authors.lastname: Levy
authors.affiliation: INSERM, Université Paris-Sud, Institut André Lwoff, 94807 Villejuif, France;
authors.forename: Claude
authors.initials: C
authors.lastname: Boucheix
authors.affiliation: INSERM, Université Paris-Sud, Institut André Lwoff, 94807 Villejuif, France;
authors.forename: Eric
authors.initials: E
authors.lastname: Rubinstein
authors.affiliation: Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain;
authors.forename: María
authors.initials: M
authors.lastname: Minguito de la Escalera
authors.affiliation: Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain;
authors.forename: Leticia
authors.initials: L
authors.lastname: González-Cintado
authors.affiliation: Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain;
authors.forename: Carlos
authors.initials: C
authors.lastname: Ardavín
authors.affiliation: Unidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; and.
authors.forename: Esteban
authors.initials: E
authors.lastname: Veiga
authors.affiliation: Unidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; and.
authors.forename: María
authors.initials: M
authors.lastname: Yáñez-Mó
authors.affiliation: Departamento de Biología Vascular e Inflamación, Fundación Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; Servicio de Inmunología, Hospital de la Princesa, Instituto de Investigación Sanitaria Princesa, 28006 Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism*; D008087:Listeria / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis; D010766:Phosphorylation; D011485:Protein Binding; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*; D060225:Tetraspanin 28 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D050794:STAT1 Transcription Factor; D060225:Tetraspanin 28; D014409:Tumor Necrosis Factor-alpha; D053633:Receptor, Interferon alpha-beta; D009569:Nitric Oxide; D020744:rac GTP-Binding Proteins