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Università della Svizzera italiana

Influenza vaccination induces NK-cell-mediated type-II IFN response that regulates humoral immunity in an IL-6-dependent manner

Farsakoglu, Yagmur ; Palomino-Segura, Miguel ; Latino, Irene ; Zanaga, Silvia ; Chatziandreou, Nikolaos ; Pizzagalli, Diego Ulisse ; Rinaldi, Andrea ; Bolis, Marco ; Sallusto, Federica ; Stein, Jens V. ; Gonzalez, Santiago F.

In: Cell reports, 2019, vol. 26, no. 9, p. 2307-2315.e5

The role of natural killer (NK) cells in the immune response against vaccines is not fully understood. Here, we examine the function of infiltrated NK cells in the initiation of the inflammatory response triggered by inactivated influenza virus vaccine in the draining lymph node (LN). We observed that, following vaccination, NK cells are recruited to the interfollicular and medullary areas of...

Università della Svizzera italiana

Macrophage death following influenza vaccination initiates the inflammatory response that promotes dendritic cell function in the draining lymph node

Chatziandreou, Nikolaos ; Farsakoglu, Yagmur ; Palomino-Segura, Miguel ; D’Antuono, Rocco ; Pizzagalli, Diego Ulisse ; Sallusto, Federica ; Lukacs-Kornek, Veronika ; Uguccioni, Mariagrazia ; Corti, Davide ; Turley, Shannon J. ; Lanzavecchia, Antonio ; Carroll, Michael C. ; Gonzalez, Santiago F.

In: Cell reports, 2017, vol. 18, no. 10, p. 2427-2440

The mechanism by which inflammation influences the adaptive response to vaccines is not fully understood. Here, we examine the role of lymph node macrophages (LNMs) in the induction of the cytokine storm triggered by inactivated influenza virus vaccine. Following vaccination, LNMs undergo inflammasome-independent necrosis-like death that is reliant on MyD88 and Toll-like receptor 7 (TLR7)...

Università della Svizzera italiana

Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells

Ronchi, Francesca ; Basso, Camilla ; Preite, Silvia ; Reboldi, Andrea ; Baumjohann, Dirk ; Perlini, Luana ; Lanzavecchia, Antonio ; Sallusto, Federica

In: Nature communications, 2016, vol. 7, p. 11541

CD4+ Th17 are heterogeneous in terms of cytokine production and capacity to initiate autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE). Here we demonstrate that experimental priming of encephalitogenic Th cells expressing RORγt and T-bet and producing IL-17A, IFN-γ and GM-CSF but not IL-10 (Th1/Th17), is dependent on the presence of pertussis toxin (PTX) at the...

Università della Svizzera italiana

Antigen-specific Th17 cells are primed by distinct and complementary dendritic cell subsets in oropharyngeal candidiasis

Trautwein-Weidner, Kerstin ; Gladiator, André ; Kirchner, Florian R. ; Becattini, Simone ; Rülicke, Thomas ; Sallusto, Federica ; LeibundGut-Landmann, Salomé

In: PLoS pathogens, 2015, vol. 11, no. 10, p. e1005164

Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated...

Università della Svizzera italiana

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

Zohar, Yaniv ; Wildbaum, Gizi ; Novak, Rostislav ; Salzman, Andrew L. ; Thelen, Marcus ; Alon, Ronen ; Barsheshet, Yiftah ; Karp, Christopher L. ; Karin, Nathan

In: The journal of clinical investigation, 2014, vol. 124, no. 5, p. 2009-2022

A single G protein–coupled receptor (GPCR) can activate multiple signaling cascades based on the binding of different ligands. The biological relevance of this feature in immune regulation has not been evaluated. The chemokine-binding GPCR CXCR3 is preferentially expressed on CD4+ T cells, and canonically binds 3 structurally related chemokines: CXCL9, CXCL10, and CXCL11. Here we have shown...

Università della Svizzera italiana

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

Zohar, Yaniv ; Wildbaum, Gizi ; Novak, Rostislav ; Salzman, Andrew L. ; Thelen, Marcus ; Alon, Ronen ; Barsheshet, Yiftah ; Karp, Christopher L. ; Karin, Nathan

In: The journal of clinical investigation, 2018, vol. 128, no. 3, p. 1200-1201

A single G protein–coupled receptor (GPCR) can activate multiple signaling cascades based on the binding of different ligands. The biological relevance of this feature in immune regulation has not been evaluated. The chemokine-binding GPCR CXCR3 is preferentially expressed on CD4+ T cells, and canonically binds 3 structurally related chemokines: CXCL9, CXCL10, and CXCL11. Here we have shown...

Università della Svizzera italiana

Role of CXCL13 and CCL20 in the recruitment of B cells to inflammatory foci in chronic arthritis

Armas-González, Estefanía ; Domínguez-Luis, María Jesús ; Díaz-Martín, Ana ; Arce-Franco, Mayte ; Castro-Hernández, Javier ; Danelon, Gabriela ; Hernández-Hernández, Vanesa ; Bustabad-Reyes, Sagrario ; Cantabrana, Alberto ; Uguccioni ; Díaz-González, Federico

In: Arthritis research & therapy, 2018, vol. 20, p. 114

Background: B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors. Methods: Expression levels of...

Università della Svizzera italiana

Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C

Gómez, Carmen Elena ; Perdiguero, Beatriz ; Jiménez, Victoria ; Filali-Mouhim, Abdelali ; Ghneim, Khader ; Haddad, Elias K. ; Quakkerlaar, Esther D. ; Delaloye, Julie ; Harari, Alexandre ; Roger, Thierry ; Dunhen, Thomas ; Sékaly, Rafick P. ; Melief, Cornelis J. M. ; Calandra, Thierry ; Sallusto, Federica ; Lanzavecchia, Antonio ; Wagner, Ralf ; Pantaleo, Giuseppe ; Esteban, Mariano

In: Plos one, 2012, vol. 7, no. 4, p. e35485

Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1...

Università della Svizzera italiana

Chemokine heterocomplexes and cancer : A novel chapter to be written in tumor immunity

D'Agostino, Gianluca ; Cecchinato, Valentina ; Uguccioni, Mariagrazia

In: Frontiers in immunology, 2018, vol. 9, p. 2185

Infiltrating immune cells are a key component of the tumor microenvironment and play central roles in dictating tumor fate, either promoting anti-tumor immune responses, or sustaining tumor growth, angiogenesis and metastasis. A distinctive microenvironment is often associated to different tumor types, with substantial differences in prognosis. The production of a variety of chemotactic...

Università della Svizzera italiana

Redox-mediated mechanisms fuel monocyte responses to CXCL12/HMGB1 in active rheumatoid arthritis

Cecchinato, Valentina ; D'Agostino, Gianluca ; Raeli, Lorenzo ; Nerviani, Alessandra ; Schiraldi, Milena ; Danelon, Gabriela ; Manzo, Antonio ; Thelen, Marcus ; Ciurea, Adrian ; Bianchi, Marco E. ; Rubartelli, Anna ; Pitzalis, Costantino ; Uguccioni, Mariagrazia

In: Frontiers in immunology, 2018, vol. 9, p. 2118

Chemokine synergy-inducing molecules are emerging as regulating factors in cell migration. The alarmin HMGB1, in its reduced form, can complex with CXCL12 enhancing its activity on monocytes via the chemokine receptor CXCR4, while the form containing a disulfide bond, by binding to TLR2 or TLR4, initiates a cascade of events leading to production of cytokines and chemokines. So far, the...