51 results on '"Zanoni, Ivan"'
Search Results
2. Homodimeric Granzyme A Opsonizes Mycobacterium tuberculosis and Inhibits Its Intracellular Growth in Human Monocytes via Toll-Like Receptor 4 and CD14.
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Rasi, Valerio, Phelps, Kathleen R, Paulson, Keegan R, Eickhoff, Christopher S, Chinnaraj, Mathivanan, Pozzi, Nicola, Gioia, Marco Di, Zanoni, Ivan, Shakya, Shubha, Carlson, Haley L, Ford, David A, Kolar, Grant R, and Hoft, Daniel F
- Abstract
Mycobacterium tuberculosis (Mtb)-specific γ9δ2 T cells secrete granzyme A (GzmA) protective against intracellular Mtb growth. However, GzmA-enzymatic activity is unnecessary for pathogen inhibition, and the mechanisms of GzmA-mediated protection remain unknown. We show that GzmA homodimerization is essential for opsonization of mycobacteria, altered uptake into human monocytes, and subsequent pathogen clearance within the phagolysosome. Although monomeric and homodimeric GzmA bind mycobacteria, only homodimers also bind cluster of differentiation 14 (CD14) and Toll-like receptor 4 (TLR4). Without access to surface-expressed CD14 and TLR4, GzmA fails to inhibit intracellular Mtb. Upregulation of Rab11FIP1 was associated with inhibitory activity. Furthermore, GzmA colocalized with and was regulated by protein disulfide isomerase AI (PDIA1), which cleaves GzmA homodimers into monomers and prevents Mtb inhibitory activity. These studies identify a previously unrecognized role for homodimeric GzmA structure in opsonization, phagocytosis, and elimination of Mtb in human monocytes, and they highlight PDIA1 as a potential host-directed therapy for prevention and treatment of tuberculosis, a major human disease. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Vaccination against influenza viruses reduces infection, not hospitalization or death, from respiratory COVID‐19: A systematic review and meta‐analysis.
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Pontiroli, Antonio E., Scovenna, Francesco, Carlini, Valentina, Tagliabue, Elena, Martin‐Delgado, Jimmy, La Sala, Lucia, Tanzi, Elisabetta, and Zanoni, Ivan
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SARS-CoV-2 ,MEDICAL personnel ,VIRUS diseases ,INFLUENZA vaccines ,INFLUENZA viruses - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) causes COVID‐19 and has brought a huge burden in terms of human lives. Strict social distance and influenza vaccination have been recommended to avoid co‐infections between influenza viruses and SARS‐CoV‐2. Scattered reports suggested a protective effect of influenza vaccine on COVID‐19 development and severity. We analyzed 51 studies on the capacity of influenza vaccination to affect infection with SARS‐CoV‐2, hospitalization, admission to Intensive Care Units (ICU), and mortality. All subjects taken into consideration did not receive any anti‐SARS‐CoV‐2 vaccine, although their status with respect to previous infections with SARS‐CoV‐2 is not known. Comparison between vaccinated and not‐vaccinated subjects for each of the four endpoints was expressed as odds ratio (OR), with 95% confidence intervals (CIs); all analyses were performed by DerSimonian and Laird model, and Hartung‐Knapp model when studies were less than 10. In a total of 61 029 936 subjects from 33 studies, influenza vaccination reduced frequency of SARS‐CoV‐2 infection [OR plus 95% CI = 0.70 (0.65−0.77)]. The effect was significant in all studies together, in health care workers and in the general population; distance from influenza vaccination and the type of vaccine were also of importance. In 98 174 subjects from 11 studies, frequency of ICU admission was reduced with influenza vaccination [OR (95% CI) = 0.71 (0.54−0.94)]; the effect was significant in all studies together, in pregnant women and in hospitalized subjects. In contrast, in 4 737 328 subjects from 14 studies hospitalization was not modified [OR (95% CI) = 1.05 (0.82−1.35)], and in 4 139 660 subjects from 19 studies, mortality was not modified [OR (95% CI) = 0.76 (0.26−2.20)]. Our study emphasizes the importance of influenza vaccination in the protection against SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Immunobiology of Carbohydrates: Implications for Novel Vaccine and Adjuvant Design Against Infectious Diseases.
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Stefanetti, Giuseppe, Borriello, Francesco, Richichi, Barbara, Zanoni, Ivan, and Lay, Luigi
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COMMUNICABLE diseases ,CARBOHYDRATES ,CARBOHYDRATE-binding proteins ,IMMUNOLOGY ,BACTERIAL vaccines ,CARBOHYDRATE content of food - Abstract
Carbohydrates are ubiquitous molecules expressed on the surface of nearly all living cells, and their interaction with carbohydrate-binding proteins is critical to many immunobiological processes. Carbohydrates are utilized as antigens in many licensed vaccines against bacterial pathogens. More recently, they have also been considered as adjuvants. Interestingly, unlike other types of vaccines, adjuvants have improved immune response to carbohydrate-based vaccine in humans only in a few cases. Furthermore, despite the discovery of many new adjuvants in the last years, aluminum salts, when needed, remain the only authorized adjuvant for carbohydrate-based vaccines. In this review, we highlight historical and recent advances on the use of glycans either as vaccine antigens or adjuvants, and we review the use of currently available adjuvants to improve the efficacy of carbohydrate-based vaccines. A better understanding of the mechanism of carbohydrate interaction with innate and adaptive immune cells will benefit the design of a new generation of glycan-based vaccines and of immunomodulators to fight both longstanding and emerging diseases. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Inositol 1,4,5-trisphosphate 3-kinase B promotes Ca2+ mobilization and the inflammatory activity of dendritic cells.
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Marongiu, Laura, Mingozzi, Francesca, Cigni, Clara, Marzi, Roberta, Di Gioia, Marco, Garrè, Massimiliano, Parazzoli, Dario, Sironi, Laura, Collini, Maddalena, Sakaguchi, Reiko, Morii, Takashi, Crosti, Mariacristina, Moro, Monica, Schurmans, Stéphane, Catelani, Tiziano, Rotem, Rany, Colombo, Miriam, Shears, Stephen, Prosperi, Davide, and Zanoni, Ivan
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DENDRITIC cells ,INOSITOL ,PHOSPHOLIPASE C ,TRANSCRIPTION factors ,EDEMA - Abstract
Inflamed by IP4: Bacterial lipopolysaccharide (LPS) elicits inflammation in part by stimulating Ca
2+ mobilization in dendritic cells (DCs), which leads to nuclear localization of the proinflammatory transcription factor NFAT. Marongiu et al. found that LPS-induced nuclear translocation of NFAT in mouse and human DCs depended on Ca2+ influx triggered by the second messenger inositol 1,3,4,5-tetrakisphosphate (IP4 ) produced by the kinase ITPKB. IP4 stimulated the Ca2+ channel IP3 R3, which colocalized with ITPKB and the LPS co-receptor CD14 on the plasma membrane. In mice, interfering with this mechanism reduced LPS-induced vascular leakage and inflammatory arthritis. These findings suggest that interfering with the ITPKB-mediated production of IP4 is a potential strategy for treating inflammation driven by DCs. Innate immune responses to Gram-negative bacteria depend on the recognition of lipopolysaccharide (LPS) by a receptor complex that includes CD14 and TLR4. In dendritic cells (DCs), CD14 enhances the activation not only of TLR4 but also that of the NFAT family of transcription factors, which suppresses cell survival and promotes the production of inflammatory mediators. NFAT activation requires Ca2+ mobilization. In DCs, Ca2+ mobilization in response to LPS depends on phospholipase C γ2 (PLCγ2), which produces inositol 1,4,5-trisphosphate (IP3 ). Here, we showed that the IP3 receptor 3 (IP3 R3) and ITPKB, a kinase that converts IP3 to inositol 1,3,4,5-tetrakisphosphate (IP4 ), were both necessary for Ca2+ mobilization and NFAT activation in mouse and human DCs. A pool of IP3 R3 was located on the plasma membrane of DCs, where it colocalized with CD14 and ITPKB. Upon LPS binding to CD14, ITPKB was required for Ca2+ mobilization through plasma membrane–localized IP3 R3 and for NFAT nuclear translocation. Pharmacological inhibition of ITPKB in mice reduced both LPS-induced tissue swelling and the severity of inflammatory arthritis to a similar extent as that induced by the inhibition of NFAT using nanoparticles that delivered an NFAT-inhibiting peptide specifically to phagocytic cells. Our results suggest that ITPKB may represent a promising target for anti-inflammatory therapies that aim to inhibit specific DC functions. [ABSTRACT FROM AUTHOR]- Published
- 2021
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6. Dooming Phagocyte Responses: Inflammatory Effects of Endogenous Oxidized Phospholipids.
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Di Gioia, Marco and Zanoni, Ivan
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PHOSPHOLIPIDS ,PHAGOCYTES ,INFLAMMATION ,DENDRITIC cells ,IMMUNE response - Abstract
Endogenous oxidized phospholipids are produced during tissue stress and are responsible for sustaining inflammatory responses in immune as well as non-immune cells. Their local and systemic production and accumulation is associated with the etiology and progression of several inflammatory diseases, but the molecular mechanisms that underlie the biological activities of these oxidized phospholipids remain elusive. Increasing evidence highlights the ability of these stress mediators to modulate cellular metabolism and pro-inflammatory signaling in phagocytes, such as macrophages and dendritic cells, and to alter the activation and polarization of these cells. Because these immune cells serve a key role in maintaining tissue homeostasis and organ function, understanding how endogenous oxidized lipids reshape phagocyte biology and function is vital for designing clinical tools and interventions for preventing, slowing down, or resolving chronic inflammatory disorders that are driven by phagocyte dysfunction. Here, we discuss the metabolic and signaling processes elicited by endogenous oxidized lipids and outline new hypotheses and models to elucidate the impact of these lipids on phagocytes and inflammation. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Deep-sea microbes as tools to refine the rules of innate immune pattern recognition.
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Gauthier, Anna E., Chandler, Courtney E., Poli, Valentina, Gardner, Francesca M., Tekiau, Aranteiti, Smith, Richard, Bonham, Kevin S., Cordes, Erik E., Shank, Timothy M., Zanoni, Ivan, Goodlett, David R., Biller, Steven J., Ernst, Robert K., Rotjan, Randi D., and Kagan, Jonathan C.
- Abstract
Deep-sea microbes exhibit immunosilence: The innate immune system of mammals uses pattern recognition receptors (PRRs) to detect conserved ligands displayed by potentially pathogenic microbes. To probe the performance of mammalian PRRs when confronted with microbes from a largely foreign ecosystem, Gauthier et al. isolated culturable bacteria from deep-sea Pacific Ocean water samples. Most isolates obtained were Gram-negative Gammaproteobacteria from the Moritella genus. The form of the prototype PRR agonist lipopolysaccharide (LPS) found in the outer membrane of most deep-sea Moritella strains was deficient at engaging with mouse and human LPS-sensing PRRs despite retaining most structural features of LPS from human intestinal E. coli. These findings reveal that the broad recognition powers of PRRs have boundaries that can be violated by a subset of microbes recovered from extreme environments. The assumption of near-universal bacterial detection by pattern recognition receptors is a foundation of immunology. The limits of this pattern recognition concept, however, remain undefined. As a test of this hypothesis, we determined whether mammalian cells can recognize bacteria that they have never had the natural opportunity to encounter. These bacteria were cultivated from the deep Pacific Ocean, where the genus Moritella was identified as a common constituent of the culturable microbiota. Most deep-sea bacteria contained cell wall lipopolysaccharide (LPS) structures that were expected to be immunostimulatory, and some deep-sea bacteria activated inflammatory responses from mammalian LPS receptors. However, LPS receptors were unable to detect 80% of deep-sea bacteria examined, with LPS acyl chain length being identified as a potential determinant of immunosilence. The inability of immune receptors to detect most bacteria from a different ecosystem suggests that pattern recognition strategies may be defined locally, not globally. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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8. Type III interferons disrupt the lung epithelial barrier upon viral recognition.
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Broggi, Achille, Ghosh, Sreya, Sposito, Benedetta, Spreafico, Roberto, Balzarini, Fabio, Cascio, Antonino Lo, Clementi, Nicola, De Santis, Maria, Mancini, Nicasio, Granucci, Francesca, and Zanoni, Ivan
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- 2020
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9. Bariatric surgery, compared to medical treatment, reduces morbidity at all ages but does not reduce mortality in patients aged < 43 years, especially if diabetes mellitus is present: a post hoc analysis of two retrospective cohort studies
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Pontiroli, Antonio E., Ceriani, Valerio, Tagliabue, Elena, Zakaria, Ahmed S., Veronelli, Annamaria, Folli, Franco, and Zanoni, Ivan
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BARIATRIC surgery ,THERAPEUTICS ,DIABETES ,PEOPLE with diabetes ,GLYCEMIC control - Abstract
Background and aims: Bariatric surgery (BS) reduces long-term mortality in comparison with medical treatment of obesity. Some studies indicate that this effect is significant for patients above mean age in different cohorts, but not for younger patients. These findings raise the question whether morbid obese patients should undergo BS as soon as possible, or whether patients might undergo surgery later in their life. Methods: We performed a post hoc analysis of two studies; we evaluated surgery-related long-term mortality in: (1) the whole cohort [857 surgery patients (163 diabetes) vs. 2086 controls (512 diabetes)]; (2) patients above mean age [> 43 years, 427 surgery patients (133 diabetes) vs. 1054 controls (392 diabetes)]; (3) patients below mean age [≤ 43 years, 432 surgery patients (30 diabetes) vs. 1032 controls (120 diabetes]. Then, we analyzed age-related long-term mortality in the whole cohort, as well as in surgery patients and in controls. Finally, we analyzed incident diseases (diabetes, cardiovascular disease, and cancer) as a function of surgery versus no-surgery and of mean age. Results: Surgery patients, compared with controls receiving standard medical/dietary treatment, had reduced mortality in the whole cohort (HR = 0.45, 95% CI 0.33–0.62, p = 0.001) and in the study group aged > 43 years (HR = 0.39, 95% CI 0.28–0.56, p = 0.001), but not in the study group aged ≤ 43 years (HR = 0.87, 95% CI 0.42–1.80, p = 0.711). Reduced mortality was observed in non-diabetic and diabetic patients aged > 43 years (HR = 0.37, 95% CI 0.23–0.62, p = 0.001 and HR = 0.45, 95% CI 0.27–0.74, p = 0.002, respectively) who underwent bariatric surgery. In contrast, in patients aged ≤ 43 years, no significant protective effect of bariatric surgery appeared in non-diabetic patients (HR = 0.64, 95% CI 0.24–1.71, p = 0.371), and mortality increased, almost significantly, in diabetic patients aged < 43 years (HR = 2.87, 95% CI 0.96–8.56, p = 0.058), and even more in diabetic patients aged 33–43 years; HR = 4.99, 95% CI 1.18–21.09, p = 0.029). As expected, age-related mortality was increased in the whole cohort (HR = 7.23, 95% CI 5.14–10.17, p = 0.001), in non-diabetic and diabetic controls (HR = 8.55, 95% CI 5.77–12.68, p = 0.001, and HR = 3.76, 95% CI 1.97–7.18, p = 0.001, respectively). The effect of aging was slightly reduced in surgery patients (HR = 3.76, 95% CI 1.87–7.58, p = 0.001), while it was not significant in diabetic surgery patients (HR = 0.70, 95% CI 0.26–1.90, p = 0.88), further emphasizing that diabetes per se has a strong negative effect on survival, also with concomitant bariatric surgery. In a supplementary analysis, HRs did not change when surgery and control parents were matched for the presence of diabetes. Incident diseases (cardiovascular, diabetes, and cancer) were less frequent in surgery than in control patients, irrespective of age. Conclusion: Bariatric surgery reduces long-term mortality in comparison with medical treatment when performed in patients aged > 43 years, but not in younger patients, where it is neutral or could even increase mortality; reduction in morbidity occurs at any age. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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10. Cellular and molecular mechanisms of antifungal innate immunity at epithelial barriers: The role of C‐type lectin receptors.
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Borriello, Francesco, Zanoni, Ivan, and Granucci, Francesca
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NATURAL immunity ,FUNGAL cell walls ,PATTERN perception receptors ,PLANT-fungus relationships ,MYCOSES ,DISEASE susceptibility - Abstract
Humans are constantly exposed to fungi, either in the form of commensals at epithelial barriers or as inhaled spores. Innate immune cells play a pivotal role in maintaining commensal relationships and preventing skin, mucosal, or systemic fungal infections due to the expression of pattern recognition receptors that recognize fungal cell wall components and modulate both their activation status and the ensuing adaptive immune response. Commensal fungi also play a critical role in the modulation of homeostasis and disease susceptibility at epithelial barriers. This review will outline cellular and molecular mechanisms of anti‐fungal innate immunity focusing on C‐type lectin receptors and their relevance in the context of host‐fungi interactions at skin and mucosal surfaces in murine experimental models as well as patients susceptible to fungal infections. [ABSTRACT FROM AUTHOR]
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- 2020
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11. Are nanotechnological approaches the future of treating inflammatory diseases?
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Rizzuto, Maria Antonietta, Salvioni, Lucia, Rotem, Rany, Colombo, Miriam, Zanoni, Ivan, Granucci, Francesca, and Prosperi, Davide
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The current treatments for chronic inflammatory diseases cause severe side effects due to nonspecific drug accumulation. Nanotechnology opens the way to new therapeutic strategies that exploit the ability of immune cells, and especially of phagocytes, to internalize nanoparticles. The cellular uptake of nanoparticles requires specific interactions and is affected by the chemical and physical properties of the carriers. Therefore, optimizing these properties is crucial for designing nanodrugs for immunotherapy. In perspective, we discuss the nanoparticle-based approaches that have been proposed to induce tolerance in autoimmune disorders and lessen the symptoms of inflammatory diseases. [ABSTRACT FROM AUTHOR]
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- 2019
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12. Below the surface: The inner lives of TLR4 and TLR9.
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Marongiu, Laura, Gornati, Laura, Artuso, Irene, Zanoni, Ivan, and Granucci, Francesca
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IMMUNOREGULATION ,PATTERN perception receptors ,TRAFFIC engineering ,INFLAMMATORY mediators ,CELL membranes - Abstract
TLRs are a class of pattern recognition receptors (PRRs) that detect invading microbes by recognizing pathogen‐associated molecular patterns (PAMPs). Upon PAMP engagement, TLRs activate a signaling cascade that leads to the production of inflammatory mediators. The localization of TLRs, either on the plasma membrane or in the endolysosomal compartment, has been considered to be a fundamental aspect to determine to which ligands the receptors bind, and which transduction pathways are induced. However, new observations have challenged this view by identifying complex trafficking events that occur upon TLR‐ligand binding. These findings have highlighted the central role that endocytosis and receptor trafficking play in the regulation of the innate immune response. Here, we review the TLR4 and TLR9 transduction pathways and the importance of their different subcellular localization during the inflammatory response. Finally, we discuss the implications of TLR9 subcellular localization in autoimmunity. [ABSTRACT FROM AUTHOR]
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- 2019
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13. Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines.
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Gornati, Laura, Zanoni, Ivan, and Granucci, Francesca
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DENDRITIC cells ,IMMUNE response ,ANTINEOPLASTIC agents - Abstract
Vaccines represent the discovery of utmost importance for global health, due to both prophylactic action to prevent infections and therapeutic intervention in neoplastic diseases. Despite this, current vaccination strategies need to be refined to successfully generate robust protective antigen-specific memory immune responses. To address this issue, one possibility is to exploit the high efficiency of dendritic cells (DCs) as antigen-presenting cells for T cell priming. DCs functional plasticity allows shaping the outcome of immune responses to achieve the required type of immunity. Therefore, the choice of adjuvants to guide and sustain DCs maturation, the design of multifaceted vehicles, and the choice of surface molecules to specifically target DCs represent the key issues currently explored in both preclinical and clinical settings. Here, we review advances in DCs-based vaccination approaches, which exploit direct
in vivo DCs targeting and activation options. We also discuss the recent findings for efficient antitumor DCs-based vaccinations and combination strategies to reduce the immune tolerance promoted by the tumor microenvironment. [ABSTRACT FROM AUTHOR]- Published
- 2018
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14. Interferon (IFN)-λ Takes the Helm: Immunomodulatory Roles of Type III IFNs.
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Zanoni, Ivan, Granucci, Francesca, and Broggi, Achille
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INTERFERONS ,IMMUNOMODULATORS ,HOMOLOGY (Biology) - Abstract
Type III interferons (IFNs) (or IFN-λ) are the latest addition to the IFN family. Even though they share little protein homology with type I IFN, both exhibit remarkable functional similarities: each can be induced in response to viral infections, and both lead to Janus kinases (JAK) and signal transducer and activator of transcription (STAT) activation. The JAK/STAT pathway induces antiviral responses and IFN-stimulated gene transcription. However, despite the similarities in their effector functions with type I IFNs, IFN-λ also has a non-redundant role in protecting barrier organs: epithelial cells preferentially produce IFN-λ rather than type I IFNs; and interferon lambda receptor 1 (IFNLR1), the specific receptor for IFN-λ, is highly expressed on cells of epithelial lineage. Thus far, IFN-λ has been considered mainly as an epithelial cytokine, which restricts viral replication in epithelial cells and constitutes an added layer of protection at mucosal sites. However, it is now increasingly recognized that IFNLR1 is expressed broadly, and that immune cells such as neutrophils and dendritic cells also respond to IFN-λ. Moreover, in many in vivo models, IFN-λ modulates immune cell functions and thereby configures itself less as a cytokine that is only specific to the epithelium, and more as a cytokine that directly controls the inflammatory response at mucosal sites. Here, we critically review the recent literature on immune modulatory roles for IFN-λ, and distinguish between the direct and indirect effects of this IFN on immune cell functions in different inflammatory settings. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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15. Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems.
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Santus, William, Barresi, Simona, Mingozzi, Francesca, Broggi, Achille, Orlandi, Ivan, Stamerra, Giulia, Vai, Marina, Martorana, Alessandra M., Polissi, Alessandra, Köhler, Julia R., Liu, Ningning, Zanoni, Ivan, and Granucci, Francesca
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Nuclear factor of activated T cells (NFAT) is activated in innate immune cells downstream of pattern recognition receptors, but little is known about NFAT’s functions in innate immunity compared with adaptive immunity. We show that early activation of NFAT balances the two major phases of the innate response to Candida albicans skin infections: the protective containment (abscess) and the elimination (expulsion) phases. During the early containment phase, transforming growth factor–β (TGF-β) induces the deposit of collagen around newly recruited polymorphonuclear cells to prevent microbial spreading. During the elimination phase, interferon-γ (IFN-γ) blocks differentiation of fibroblasts into myofibroblasts by antagonizing TGF-β signaling. IFN-γ also induces the formation of plasmin that, in turn, promotes abscess capsule digestion and skin ulceration for microbial discharge. NFAT controls innate IFN-γ production and microbial expulsion. This cross-talk between the innate immune and the fibrinolytic systems also occurs during infection with Staphylococcus aureus and is a protective response to minimize tissue damage and optimize pathogen elimination. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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16. Prolonged contact with dendritic cells turns lymph node-resident NK cells into anti-tumor effectors.
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Mingozzi, Francesca, Spreafico, Roberto, Gorletta, Tatiana, Cigni, Clara, Di Gioia, Marco, Caccia, Michele, Sironi, Laura, Collini, Maddalena, Soncini, Matias, Rusconi, Michela, von Andrian, Ulrich H, Chirico, Giuseppe, Zanoni, Ivan, and Granucci, Francesca
- Abstract
Natural killer ( NK) cells are critical players against tumors. The outcome of anti-tumor vaccination protocols depends on the efficiency of NK-cell activation, and efforts are constantly made to manipulate them for immunotherapeutic approaches. Thus, a better understanding of NK-cell activation dynamics is needed. NK-cell interactions with accessory cells and trafficking between secondary lymphoid organs and tumoral tissues remain poorly characterized. Here, we show that upon triggering innate immunity with lipopolysaccharide ( LPS), NK cells are transiently activated, leave the lymph node, and infiltrate the tumor, delaying its growth. Interestingly, NK cells are not actively recruited at the draining lymph node early after LPS administration, but continue their regular homeostatic turnover. Therefore, NK cells resident in the lymph node at the time of LPS administration become activated and exert anti-tumor functions. NK-cell activation correlates with the establishment of prolonged interactions with dendritic cells ( DCs) in lymph nodes, as observed by two-photon microscopy. Close DC and NK-cell contacts are essential for the localized delivery of DC-derived IL-18 to NK cells, a strict requirement in NK-cell activation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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17. Cream Formulation Impact on Topical Administration of Engineered Colloidal Nanoparticles.
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Santini, Benedetta, Zanoni, Ivan, Marzi, Roberta, Cigni, Clara, Bedoni, Marzia, Gramatica, Furio, Palugan, Luca, Corsi, Fabio, Granucci, Francesca, and Colombo, Miriam
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INFLAMMATION treatment ,NANOMEDICINE ,TREATMENT effectiveness ,TARGETED drug delivery ,COLLOIDS ,TOPICAL drug administration - Abstract
In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide) nanoparticles (MNP) coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP) cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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18. Innate Immune Pattern Recognition: A Cell Biological Perspective.
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Brubaker, Sky W., Bonham, Kevin S., Zanoni, Ivan, and Kagan, Jonathan C.
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IMMUNE response ,NATURAL immunity ,IMMUNE system ,IMMUNOLOGIC memory ,CYTOSOL - Abstract
Receptors of the innate immune system detect conserved determinants of microbial and viral origin. Activation of these receptors initiates signaling events that culminate in an effective immune response. Recently, the view that innate immune signaling events rely on and operate within a complex cellular infrastructure has become an important framework for understanding the regulation of innate immunity. Compartmentalization within this infrastructure provides the cell with the ability to assign spatial information to microbial detection and regulate immune responses. Several cell biological processes play a role in the regulation of innate signaling responses; at the same time, innate signaling can engage cellular processes as a form of defense or to promote immunological memory. In this review, we highlight these aspects of cell biology in pattern-recognition receptor signaling by focusing on signals that originate from the cell surface, from endosomal compartments, and from within the cytosol. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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19. rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant.
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Petrarca, Claudia, Clemente, Emanuela, Toto, Valentina, Lezzi, Manuela, Rossi, Cosmo, Zanotta, Stefania, Mistrello, Gianni, Zanoni, Ivan, Granucci, Francesca, Arioli, Stefania, Mora, Diego, Guglielmetti, Simone, Paganelli, Roberto, and Di Gioacchino, Mario
- Published
- 2014
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20. Wiskott- Aldrich syndrome protein deficiency in natural killer and dendritic cells affects antitumor immunity.
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Catucci, Marco, Zanoni, Ivan, Draghici, Elena, Bosticardo, Marita, Castiello, Maria C., Venturini, Massimo, Cesana, Daniela, Montini, Eugenio, Ponzoni, Maurilio, Granucci, Francesca, and Villa, Anna
- Abstract
Wiskott- Aldrich syndrome ( WAS) is a primary immunodeficiency caused by reduced or absent expression of the WAS protein ( WASP). WAS patients are affected by microthrombocytopenia, recurrent infections, eczema, autoimmune diseases, and malignancies. Although immune deficiency has been proposed to play a role in tumor pathogenesis, there is little evidence on the correlation between immune cell defects and tumor susceptibility. Taking advantage of a tumor-prone model, we show that the lack of WASP induces early tumor onset because of defective immune surveillance. Consistently, the B16 melanoma model shows that tumor growth and the number of lung metastases are increased in the absence of WASP. We then investigated the in vivo contribution of Was
−/− NK cells and DCs in controlling B16 melanoma development. We found fewer B16 metastases developed in the lungs of Was−/− mice that had received WT NK cells as compared with mice bearing Was−/− NK cells. Furthermore, we demonstrated that Was−/− DCs were less efficient in inducing NK-cell activation in vitro and in vivo. In summary, for the first time, we demonstrate in in vivo models that WASP deficiency affects resistance to tumor and causes impairment in the antitumor capacity of NK cells and DCs. [ABSTRACT FROM AUTHOR]- Published
- 2014
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21. Modulation of CD14 and TLR4⋅MD-2 Activities by a Synthetic Lipid A Mimetic.
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Cighetti, Roberto, Ciaramelli, Carlotta, Sestito, Stefania Enza, Zanoni, Ivan, Kubik, Łukasz, Ardá‐Freire, Ana, Calabrese, Valentina, Granucci, Francesca, Jerala, Roman, Martín‐Santamaría, Sonsoles, Jiménez‐Barbero, Jesus, and Peri, Francesco
- Published
- 2014
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22. Modeling Leukocyte-Leukocyte Non-Contact Interactions in a Lymph Node.
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Gritti, Nicola, Caccia, Michele, Sironi, Laura, Collini, Maddalena, D'Alfonso, Laura, Granucci, Francesca, Zanoni, Ivan, and Chirico, Giuseppe
- Subjects
LEUCOCYTES ,CELL communication ,NATURAL immunity ,IMMUNE response ,CHEMOKINES ,BIODEGRADATION ,COMPARATIVE studies - Abstract
The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines) allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field description inspired by the Keller-Segel chemotaxis model, of which we report an analytical solution suited for slowly varying sources of chemokines. Since our focus is on the non-contact interactions, leukocyte-leukocyte contact interactions are simulated only by means of a space dependent friction coefficient of the cells. The analytical solution of the Keller-Segel model is then taken as the basis of numerical simulations of interactions between leukocytes and their duration. The mean field interaction force that we derive has a time-space separable form and depends on the chemotaxis sensitivity parameter as well as on the chemokines diffusion coefficient and their degradation rate. All these parameters affect the distribution of the interaction durations. We draw a successful qualitative comparison between simulated data and sets of experimental data for DC-NK cells interaction duration and other kinematic parameters. Remarkably, the predicted percentage of the leukocyte-leukocyte interactions falls in the experimental range and depends (≅25% increase) upon the chemotactic parameter indicating a non-negligible direct effect of the non-contact interaction on the leukocyte interactions. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
23. IL-15 cis Presentation Is Required for Optimal NK Cell Activation in Lipopolysaccharide-Mediated Inflammatory Conditions.
- Author
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Zanoni, Ivan, Spreafico, Roberto, Bodio, Caterina, Di Gioia, Marco, Cigni, Clara, Broggi, Achille, Gorletta, Tatiana, Caccia, Michele, Chirico, Giuseppe, Sironi, Laura, Collini, Maddalena, Colombo, Mario P., Garbi, Natalio, and Granucci, Francesca
- Abstract
Summary: Natural killer (NK) cells have antitumor, antiviral, and antibacterial functions, and efforts are being made to manipulate them in immunotherapeutic approaches. However, their activation mechanisms remain poorly defined, particularly during bacterial infections. Here, we show that upon lipopolysaccharide or E. coli exposure, dendritic cells (DCs) produce three cytokines—interleukin 2 (IL-2), IL-18, and interferon β (IFN-β)—necessary and sufficient for NK cell activation. IFN-β enhances NK cell activation by inducing IL-15 and IL-15 receptor α not only in DCs but, surprisingly, also in NK cells. This process allows the transfer of IL-15 on NK cell surface and its cis presentation. cis-presented NK cell-derived and trans-presented DC-derived IL-15 contribute equally to optimal NK cell activation. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
24. Role of CD14 in host protection against infections and in metabolism regulation.
- Author
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Zanoni, Ivan and Granucci, Francesca
- Subjects
GLYCOSYLPHOSPHATIDYLINOSITOL ,METABOLISM ,INFECTION ,MEDICAL microbiology ,NUTRITION disorders ,PROTEINS - Abstract
CD14 is a glycosylphosphatidylinositol (GPI)-anchored receptor known to serve as a co-receptor for several Toll-like Receptors (TLRs) both at the cell surface and in the endosomal compartment. CD14 can be expressed by cells of both hematopoietic and non-hematopoietic origin as a cell membrane or secreted protein. Although CD14 was discovered more than 20 years ago, its activities remain largely to be defined. Most of the information available concerns CD14's role as a co-receptor working with TLR4 and facilitating cellular responses to low doses of lipopolysaccharide (LPS). Recent studies have highlighted and molecularly defined many other functions of this pattern recognition receptor (PRR). These functions include the mechanisms through which CD14 allows the activation of the TLR4-TRAM-TRIF pathway upon LPS stimulation; the capacity of CD14 to transduce a TLR4-independent signaling pathway leading to the activation of NFAT transcription factor family members with important consequences in myeloid cells; the CD14 influence on cell metabolism in conditions predisposing to obesity. In this review, we summarize recent progresses toward the molecular definition of the multiple roles exerted by CD14 in innate immune cells in response to LPS and the consequences of CD14 activation in physiologic and pathologic conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
25. Differential Regulation of Smad3 and of the Type II Transforming Growth Factor-β Receptor in Mitosis: Implications for Signaling.
- Author
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Neyrolles, Olivier, Pontiroli, Francesca, Dussurget, Olivier, Zanoni, Ivan, Urbano, Matteo, Beretta, Ottavio, Granucci, Francesca, Ricciardi-Castagnoli, Paola, Cossart, Pascale, and Foti, Maria
- Subjects
DENDRITIC cells ,INFECTION ,TUMORS ,LISTERIA monocytogenes ,GENE expression ,GENOMICS - Abstract
Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immunity and play a crucial role in the first phase of host defense against infections and tumors. Listeria monocytogenes (Lm) is an intracellular pathogen that colonizes the cytosol of eukaryotic cells. Recent findings have shown Lm specifically in splenic CD8a
+ DCs shortly after intravenous infection. We examined gene expression profiles of mouse DCs exposed to Lm to elucidate the molecular mechanisms underlying DCs interaction with Lm. Using a functional genomics approach, we found that Lm infection induced a cluster of late response genes including type I IFNs and interferon responsive genes (IRGs) in DCs. Type I INFs were produced at the maximal level only at 24 h post infection indicating that the regulation of IFNs in the context of Lm infection is delayed compared to the rapid response observed with viral pathogens. We showed that during Lm infection, IFNγ production and cytotoxic activity were severely impaired in NK cells compared to E. coli infection. These defects were restored by providing an exogenous source of IFNβ during the initial phase of bacterial challenge. Moreover, when treated with IFNβ during early infection, NK cells were able to reduce bacterial titer in the spleen and significantly improve survival of infected mice. These findings show that the timing of IFNβ production is fundamental to the efficient control of the bacterium during the early innate phase of Lm infection. [ABSTRACT FROM AUTHOR]- Published
- 2012
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- View/download PDF
26. Regulation and dysregulation of innate immunity by NFAT signaling downstream of pattern recognition receptors (PRRs).
- Author
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Zanoni, Ivan and Granucci, Francesca
- Abstract
Innate immunity is the most ancient form of response to pathogens and it relies on evolutionary conserved signaling pathways, i.e. those involving the NF-κ B pathway. Nevertheless, increasing evidence suggests that factors that have appeared more recently in evolution, such as the nuclear factor of activated T-cell transcription factor family ( NFATc), also contribute to innate immune-response regulation in vertebrates. Exposure to inflammatory stimuli induces the activation of NFATc factors in innate immune cells, including conventional dendritic cells ( DCs), granulocytes, mast cells and under pathological circumstances, also macrophages. While the evolutionary conserved functions of innate immunity, such as direct microbial killing and interferon production, are expected to be NFATc independent, other aspects of innate immunity, including collaboration with adaptive immunity and mechanisms to limit the tissue damage generated by the inflammatory process, are presumably controlled by NFATc members in collaboration with other transcription factors. In this article, we discuss the recent advances regarding the role of the NFATc signaling pathway in regulating DC, neutrophil and macrophage responses to specific inflammatory stimuli, including lipopolysaccharide and β-glucan-bearing microorganisms. We also discuss how NFATc signaling influences the interactions of myeloid cells with lymphocytes. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
27. Functional crosstalk between dendritic cells and Foxp3+ regulatory T cells in the maintenance of immune tolerance.
- Author
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Kornete, Mara, Piccirillo, Ciriaco A., Granucci, Francesca, and Zanoni, Ivan
- Subjects
IMMUNOLOGICAL tolerance ,DENDRITIC cells ,T cells ,IMMUNE response ,AUTOIMMUNE diseases - Abstract
Peripheral immune tolerance requires a controlled balance between the maintenance of self-tolerance and the capacity to engage protective immune responses against pathogens. Dendritic cells (DCs) serve as sentinels of the immune system by sensing environmental and inflammatory signals, and play an essential role in the maintenance of immune tolerance. To achieve this, DC play a key role in dictating the outcome of immune responses by influencing the balance between inflammatory or Foxp3
+ regulatory T (Treg ) cell responses. At the heart of this immunological balance is a finely regulated DC and Treg cell crosstalk whereby Treg cells modulate DC phenotype and function, and DC drive the differentiation of Foxp3+ Treg cells in order to control immune responses. This review will focus on recent advances, which highlight the importance of this bidirectional DC and Treg cell crosstalk during the induction of tolerance and organ-specific autoimmunity. More specifically, we will discuss how Treg cells modulate DC function for the suppression of inflammatory responses and how DC subsets employ diverse mechanisms to drive differentiation of Treg cells. Finally, we will discuss the therapeutic potential of tolerogenic DCs for the induction of tolerance in autoimmune diseases. [ABSTRACT FROM AUTHOR]- Published
- 2012
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- View/download PDF
28. Vaccination with filamentous bacteriophages targeting DEC-205 induces DC maturation and potent anti-tumor T-cell responses in the absence of adjuvants.
- Author
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Sartorius, Rossella, Bettua, Clotilde, D'Apice, Luciana, Caivano, Antonella, Trovato, Maria, Russo, Domenico, Zanoni, Ivan, Granucci, Francesca, Mascolo, Dina, Barba, Pasquale, Pozzo, Giovanna Del, and Berardinis, Piergiuseppe De
- Abstract
The efficacy of a new vaccine-delivery vector, based on the filamentous bacteriophage fd displaying a single-chain antibody fragment known to bind the mouse DC surface molecule DEC-205, is reported. We demonstrate both in vitro and in vivo an enhanced receptor-mediated uptake of phage particles expressing the anti-DEC-205 fragment by DCs. We also report that DCs targeted by fd virions in the absence of other stimuli produce IFN-α and IL-6, and acquire a mature phenotype. Moreover, DC-targeting with fd particles double-displaying the anti-DEC-205 fragment on the pIII protein and the OVA
257-264 antigenic determinant on the pVIII protein induced potent inhibition of the growth of the B16-OVA tumor in vivo. This protection was much stronger than other immunization strategies and similar to that induced by adoptively transferred DCs. Since targeting DEC-205 in the absence of DC activation/maturation agents has previously been described to result in tolerance, the ability of fd bacteriophages to induce a strong tumor-specific immune response by targeting DCs through DEC-205 is unexpected, and further validates the potential employment of this safe, versatile and inexpensive delivery system for vaccine formulation. [ABSTRACT FROM AUTHOR]- Published
- 2011
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29. The regulatory role of dendritic cells in the induction and maintenance of T-cell tolerance.
- Author
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Zanoni, Ivan and Granucci, Francesca
- Subjects
DENDRITIC cells ,T cells ,BIOCOMPATIBILITY ,INTERLEUKIN-2 ,AUTOIMMUNITY ,CYTOLOGY ,ANTIGENS - Abstract
The induction and maintenance of T-cell tolerance to tissue antigens is essential to prevent autoimmunity. Combinations of central and peripheral mechanisms act in parallel to inactivated, eliminated or control autoreactive T cells. Both centrally and peripherally, a key requirement for self-tolerance is the presentation of self-antigens in a correct context. There is now evidence to suggest that dendritic cells (DCs) play a fundamental role in the development of central and peripheral tolerance. In this review, we summarize recent progress toward the definition of the multiple roles of DCs in these processes. We will also discuss the association between defects in the DC compartment and the development of autoimmune responses, with particular reference to DC deregulation in the context of type I diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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- View/download PDF
30. Uniform Lipopolysaccharide (LPS)-Loaded Magnetic Nanoparticles for the Investigation of LPS-TLR4 Signaling.
- Author
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Piazza, Matteo, Colombo, Miriam, Zanoni, Ivan, Granucci, Francesca, Tortora, Paolo, Weiss, Jerrold, Gioannini, Theresa, Prosperi, Davide, and Peri, Francesco
- Published
- 2011
- Full Text
- View/download PDF
31. Uniform Lipopolysaccharide (LPS)-Loaded Magnetic Nanoparticles for the Investigation of LPS-TLR4 Signaling.
- Author
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Piazza, Matteo, Colombo, Miriam, Zanoni, Ivan, Granucci, Francesca, Tortora, Paolo, Weiss, Jerrold, Gioannini, Theresa, Prosperi, Davide, and Peri, Francesco
- Published
- 2011
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- View/download PDF
32. Deciphering the complexity of Toll-like receptor signaling.
- Author
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Ostuni, Renato, Zanoni, Ivan, and Granucci, Francesca
- Subjects
IMMUNE response ,POST-translational modification ,CELLULAR signal transduction ,APOPTOSIS ,DENDRITIC cells ,UBIQUITIN ,NATURAL immunity - Abstract
Toll-like receptors (TLRs) are essential players in the innate immune response to invading pathogens. Although extensive research efforts have provided a considerable wealth of information on how TLRs function, substantial gaps in our knowledge still prevent the definition of a complete picture of TLR signaling. However, several recent studies describe additional layers of complexity in the regulation of TLR ligand recognition, adaptor recruitment, posttranslational modifications of signaling proteins, and the newly described, autonomous role of the TLR4 co-receptor CD14. In this review, by using it as model system for the whole TLR family, we attempt to provide a complete description of the signal transduction pathways triggered by TLR4, with a particular emphasis on the molecular and cell biological aspects regulating its function. Finally, we discuss a recently reported model of CD14-dependent signaling and highlight its biological implications. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
33. Regulation of antigen uptake, migration, and lifespan of dendritic cell by Toll-like receptors.
- Author
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Zanoni, Ivan and Granucci, Francesca
- Subjects
ANTIGENS ,PATHOGENIC microorganisms ,ENDOCYTOSIS ,LYMPHOCYTES ,LYMPHOID tissue - Abstract
Dendritic cells (DCs) sense the presence of pathogens through germline-encoded pattern recognition receptors (PRRs), which recognize molecular patterns expressed by various microorganisms and endogenous stimuli. Toll-like receptors (TLRs) are the best characterized PRRs. TLR activation has a profound effect on a number of DC activities, including endocytosis, cytoskeleton rearrangement, migration, antigen processing and presentation, survival, and death. The goal of TLR-induced DC reprogramming is to promote the appropriate activation and differentiation of lymphocytes bearing clonally distributed antigen-specific receptors. In this review, we will focus on the functional consequences of TLR engagement for conventional DCs. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
34. Accumulative Difference Image Protocol for Particle Tracking in Fluorescence Microscopy Tested in Mouse Lymphonodes.
- Author
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Villa, Carlo E., Caccia, Michele, Sironi, Laura, D'Alfonso, Laura, Collini, Maddalena, Rivolta, Ilaria, Miserocchi, Giuseppe, Gorletta, Tatiana, Zanoni, Ivan, Granucci, Francesca, and Chirico, Giuseppe
- Subjects
FLUORESCENCE microscopy ,ALGORITHMS ,IMAGE processing ,LYMPHOCYTES ,LIPIDS ,NANOPARTICLES ,LABORATORY mice ,MEDICAL protocols ,CYTOLOGICAL research ,EQUIPMENT & supplies - Abstract
The basic research in cell biology and in medical sciences makes large use of imaging tools mainly based on confocal fluorescence and, more recently, on non-linear excitation microscopy. Substantially the aim is the recognition of selected targets in the image and their tracking in time. We have developed a particle tracking algorithm optimized for low signal/ noise images with a minimum set of requirements on the target size and with no a priori knowledge of the type of motion. The image segmentation, based on a combination of size sensitive filters, does not rely on edge detection and is tailored for targets acquired at low resolution as in most of the in-vivo studies. The particle tracking is performed by building, from a stack of Accumulative Difference Images, a single 2D image in which the motion of the whole set of the particles is coded in time by a color level. This algorithm, tested here on solid-lipid nanoparticles diffusing within cells and on lymphocytes diffusing in lymphonodes, appears to be particularly useful for the cellular and the in-vivo microscopy image processing in which few a priori assumption on the type, the extent and the variability of particle motions, can be done. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
35. The dendritic cell life cycle.
- Author
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Granucci, Francesca and Zanoni, Ivan
- Published
- 2009
- Full Text
- View/download PDF
36. CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation.
- Author
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Zanoni, Ivan, Ostuni, Renato, Capuano, Giusy, Collini, Maddalena, Caccia, Michele, Ronchi, Antonella Ellena, Rocchetti, Marcella, Mingozzi, Francesca, Foti, Maria, Chirico, Giuseppe, Costa, Barbara, Zaza, Antonio, Ricciardi-Castagnoli, Paola, and Granucci, Francesca
- Subjects
LETTERS to the editor ,T cell receptors - Abstract
Toll-like receptors (TLRs) are the best characterized pattern recognition receptors. Individual TLRs recruit diverse combinations of adaptor proteins, triggering signal transduction pathways and leading to the activation of various transcription factors, including nuclear factor κB, activation protein 1 and interferon regulatory factors. Interleukin-2 is one of the molecules produced by mouse dendritic cells after stimulation by different pattern recognition receptor agonists. By analogy with the events after T-cell receptor engagement leading to interleukin-2 production, it is therefore plausible that the stimulation of TLRs on dendritic cells may lead to activation of the Ca
2+ /calcineurin and NFAT (nuclear factor of activated T cells) pathway. Here we show that mouse dendritic cell stimulation with lipopolysaccharide (LPS) induces Src-family kinase and phospholipase Cγ2 activation, influx of extracellular Ca2+ and calcineurin-dependent nuclear NFAT translocation. The initiation of this pathway is independent of TLR4 engagement, and dependent exclusively on CD14. We also show that LPS-induced NFAT activation via CD14 is necessary to cause the apoptotic death of terminally differentiated dendritic cells, an event that is essential for maintaining self-tolerance and preventing autoimmunity. Consequently, blocking this pathway in vivo causes prolonged dendritic cell survival and an increase in T-cell priming capability. Our findings reveal novel aspects of molecular signalling triggered by LPS in dendritic cells, and identify a new role for CD14: the regulation of the dendritic cell life cycle through NFAT activation. Given the involvement of CD14 in disease, including sepsis and chronic heart failure, the discovery of signal transduction pathways activated exclusively via CD14 is an important step towards the development of potential treatments involving interference with CD14 functions. [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
- View/download PDF
37. Image filtering for two-photon deep imaging of lymphonodes.
- Author
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Caccia, Michele, Sironi, Laura, Collini, Maddalena, Chirico, Giuseppe, Zanoni, Ivan, and Granucci, Francesca
- Subjects
MULTIPHOTON excitation microscopy ,INFRARED radiation ,TISSUES ,LYMPHATICS ,FOURIER analysis - Abstract
Non-linear excitation microscopy is considered an ideal spectroscopic method for imaging thick tissues in vivo due to the reduced scattering of infrared radiation. Although imaging has been reported on brain neocortex at 600–800 μm of depth, much less uniform tissues, such as lymphonodes, are characterized by highly anisotropic light scattering that limits the penetration length. We show that the most severe limitation for deep imaging of lymphonodes appears to be the tissue scattering and the diffuse fluorescence emission of labeled cell (lymphocytes) in layers above the focusing plane. We report a study of the penetration depth of the infrared radiation in a model system and in ex vivo lymphonodes and discuss the possibility to apply Fourier filtering to the images in order to improve the observation depth. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
38. Inhibition of Lipid A Stimulated Activation of Human Dendritic Cells and Macrophages by Amino and Hydroxylamino Monosaccharides.
- Author
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Peri, Francesco, Granucci, Francesca, Costa, Barbara, Zanoni, Ivan, Marinzi, Chiara, and Nicotra, Francesco
- Published
- 2007
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- View/download PDF
39. Microbiome studies in the medical sciences and the need for closer multidisciplinary interplay.
- Author
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Mancini, Nicasio, Peri, Francesco, Rescigno, Maria, and Zanoni, Ivan
- Subjects
MUCOUS membranes ,NUCLEOTIDE sequencing ,CONFERENCES & conventions ,MEDICAL sciences ,NEXT generation networks - Abstract
Next-generation sequencing techniques have enabled identification of the microorganisms colonizing mucosal tissues. The International Congress "MicrobiotaMi 2020" (Milan, February 2020) will focus on the mechanisms of microbiota-related functions in health and disease and their clinical application. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
40. Effects of dexamethazone on LPS-induced activationand migration of mouse dendritic cells revealed by a genome-wide transcriptional analysis.
- Author
-
Vizzardelli, Caterina, Pavelka, Norman, Luchini, Alessandra, Zanoni, Ivan, Bendickson, Lee, Pelizzola, Mattia, Beretta, Ottavio, Foti, Maria, Granucci, Francesca, Nilsen-Hamilton, Marit, and Ricciardi-Castagnoli, Paola
- Published
- 2006
- Full Text
- View/download PDF
41. The Regulatory Role of Dendritic Cells in the Immune Response.
- Author
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Granucci, Francesca, Zanoni, Ivan, Feau, Sonia, Capuano, Giusy, and Ricciardi-Castagnoli, Paola
- Subjects
DENDRITIC cells ,ANTIGEN presenting cells ,IMMUNE response ,IMMUNOLOGY ,INTERLEUKIN-2 - Abstract
Dendritic cells (DCs) are key regulators of immune reactions. They control early innate responses, regulate long-lasting adaptive immunity and contribute to the maintenance of self-tolerance. DCs continuously monitor the environment through a multifaceted innate antigen receptor repertoire and, in response to perturbations, start a complex genetic reprogramming that leads to a complete activation of innate and, then, adaptive immune responses. This review discusses how DCs become efficient activators of NK and, subsequently, T cells following a microbial encounter. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
42. The Immune Response Is Initiated by Dendritic Cells via Interaction with Microorganisms and Interleukin-2 Production.
- Author
-
Granucci, Francesca, Feau, Sonia, Zanoni, Ivan, Pavelka, Norman, Vizzardelli, Caterina, Raimondi, Giorgio, and Riccardi-Castagnoli, Paola
- Subjects
IMMUNE system ,IMMUNE response ,DENDRITIC cells ,INTERLEUKIN-2 ,IMMUNITY - Abstract
The immune system of vertebrate animals is characterized by the capacity to respond to disturbances. This function requires 2 different approaches. First, the immune system responds in a few hours to infectious agents (innate immunity) by recognizing molecular patterns typical of microorganisms (but absent in self-tissues). Second, it mounts a late response that differentiates among different microbes, giving rise to memory (adaptive immunity). In this context, dendritic cells (DCs) play a central role, becoming efficient stimulators of both innate and adaptive responses after microbial activation. Recent data generated by global transcriptional profiling of DCs after bacterial encounter are discussed, as are the unique DC functional plasticity and the central role of DC-derived interleukin-2 in priming early and late immune responses. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
43. Editorial: Interferon-λs: New Regulators of Inflammatory Processes.
- Author
-
Zanoni, Ivan and Odendall, Charlotte
- Subjects
INFLAMMATION ,HISTONE deacetylase ,CHRONIC hepatitis B ,MITOGEN-activated protein kinases - Abstract
It isn't until 2003 that a third family emerged, type III IFNs also known as IFN 1-4 or IL29, Il28A-C. Type III IFNs are functionally closer to type I IFNs as they have potent antiviral functions and induce a largely overlapping family of interferon stimulated genes (ISGs). These functions are best described in epithelial cells, the primary target of type III IFNs, but more recent immunomodulatory roles of type III IFNs are emerging. As a consequence, the function of type III IFNs are most important at mucosal surfaces and type III IFNs have been emerging as critical regulators of immunity at barrier sites. [Extracted from the article]
- Published
- 2019
- Full Text
- View/download PDF
44. Inflammasomes within Hyperactive Murine Dendritic Cells Stimulate Long-Lived T Cell-Mediated Anti-tumor Immunity.
- Author
-
Zhivaki, Dania, Borriello, Francesco, Chow, Ohn A., Doran, Benjamin, Fleming, Ira, Theisen, Derek J., Pallis, Paris, Shalek, Alex K., Sokol, Caroline L., Zanoni, Ivan, and Kagan, Jonathan C.
- Abstract
Central to anti-tumor immunity are dendritic cells (DCs), which stimulate long-lived protective T cell responses. Recent studies have demonstrated that DCs can achieve a state of hyperactivation, which is associated with inflammasome activities within living cells. Herein, we report that hyperactive DCs have an enhanced ability to migrate to draining lymph nodes and stimulate potent cytotoxic T lymphocyte (CTL) responses. This enhanced migratory activity is dependent on the chemokine receptor CCR7 and is associated with a unique transcriptional program that is not observed in conventionally activated or pyroptotic DCs. We show that hyperactivating stimuli are uniquely capable of inducing durable CTL-mediated anti-tumor immunity against tumors that are sensitive or resistant to PD-1 inhibition. These protective responses are intrinsic to the cDC1 subset of DCs, depend on the inflammasome-dependent cytokine IL-1β, and enable tumor lysates to serve as immunogens. If these activities are verified in humans, hyperactive DCs may impact immunotherapy. • Hyperactive dendritic cells display enhanced ability to migrate to lymph nodes • Hyperactive dendritic cells retain inflammasome activity in the dLN • Hyperactive cDC1s induce long-lived CD8
+ T-cell-mediated anti-tumor immunity • Hyperactivating stimuli eradicate tumors that are resistant to anti-PD1 therapy Inflammasome activation in dendritic cells (DCs) leads to pyroptosis or hyperactivation. Zhivaki et al. show that in contrast to pyroptotic DCs, hyperactive DCs stimulate durable anti-tumor immunity that eradicates established tumors. These protective responses are intrinsic to cDC1 cells and depend on DC hypermigration and on the inflammasome-dependent cytokine IL-1β. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
45. Luminescent conjugates between dinuclear rhenium(I) complexes and peptide nucleic acids (PNA) for cell imaging and DNA targeting.
- Author
-
Ferri, Elena, Donghi, Daniela, Panigati, Monica, Prencipe, Giuseppe, D'Alfonso, Laura, Zanoni, Ivan, Baldoli, Clara, Maiorana, Stefano, D'Alfonso, Giuseppe, and Licandro, Emanuela
- Subjects
METAL complexes ,ORGANORHENIUM compounds ,LUMINESCENCE ,PEPTIDES ,DNA ,METAL carbonyls ,SOLID-phase synthesis ,TWO-photon absorbing materials - Abstract
New luminescent dinuclear rhenium(i) tricarbonyl complexâPNA conjugates have been synthesized through a reliable solid-phase synthetic methodology. Their photophysical properties have been measured. The most luminescent ReâPNA conjugate 7showed interesting two-photon absorption (TPA) properties, that were exploited for imaging experiments, to demonstrate its easy uptake into living cells. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
46. Luminescent conjugates between dinuclear rhenium(i) complexes and peptide nucleic acids (PNA) for cell imaging and DNA targetingElectronic supplementary information (ESI) available: Acronyms of reagents and solvents, details on the synthesis and characterization of the compounds here described. See DOI: 10.1039/c0cc00450b
- Author
-
Ferri, Elena, Donghi, Daniela, Panigati, Monica, Prencipe, Giuseppe, D'Alfonso, Laura, Zanoni, Ivan, Baldoli, Clara, Maiorana, Stefano, D'Alfonso, Giuseppe, and Licandro, Emanuela
- Subjects
METAL complexes ,ORGANORHENIUM compounds ,LUMINESCENCE ,PEPTIDES ,DNA ,METAL carbonyls ,SOLID-phase synthesis ,TWO-photon absorbing materials - Abstract
New luminescent dinuclear rhenium(i) tricarbonyl complexâPNA conjugates have been synthesized through a reliable solid-phase synthetic methodology. Their photophysical properties have been measured. The most luminescent ReâPNA conjugate 7showed interesting two-photon absorption (TPA) properties, that were exploited for imaging experiments, to demonstrate its easy uptake into living cells. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
47. Luminescent conjugates between dinuclear rhenium(I) complexes and peptide nucleic acids (PNA) for cell imaging and DNA targeting.
- Author
-
Ferri, Elena, Donghi, Daniela, Panigati, Monica, Prencipe, Giuseppe, D'Alfonso, Laura, Zanoni, Ivan, Baldoli, Clara, Maiorana, Stefano, D'Alfonso, Giuseppe, and Licandro, Emanuela
- Subjects
METAL complexes ,ORGANORHENIUM compounds ,LUMINESCENCE ,PEPTIDES ,DNA ,METAL carbonyls ,SOLID-phase synthesis - Abstract
New luminescent dinuclear rhenium(i) tricarbonyl complexâPNA conjugates have been synthesized through a reliable solid-phase synthetic methodology. Their photophysical properties have been measured. The most luminescent ReâPNA conjugate 7showed interesting two-photon absorption (TPA) properties, that were exploited for imaging experiments, to demonstrate its easy uptake into living cells. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
48. Luminescent conjugates between dinuclear rhenium(i) complexes and peptide nucleic acids (PNA) for cell imaging and DNA targetingElectronic supplementary information (ESI) available: Acronyms of reagents and solvents, details on the synthesis and characterization of the compounds here described. See DOI: 10.1039/c0cc00450b
- Author
-
Ferri, Elena, Donghi, Daniela, Panigati, Monica, Prencipe, Giuseppe, D'Alfonso, Laura, Zanoni, Ivan, Baldoli, Clara, Maiorana, Stefano, D'Alfonso, Giuseppe, and Licandro, Emanuela
- Subjects
NUCLEIC acids ,SOLID-phase synthesis ,LUMINESCENCE ,TWO-photon absorbing materials ,IMAGING systems in chemistry ,ABSORPTION - Abstract
New luminescent dinuclear rhenium(i) tricarbonyl complex–PNA conjugates have been synthesized through a reliable solid-phase synthetic methodology. Their photophysical properties have been measured. The most luminescent Re–PNA conjugate 7showed interesting two-photon absorption (TPA) properties, that were exploited for imaging experiments, to demonstrate its easy uptake into living cells. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
49. The nature of activatory and tolerogenic dendritic cell-derived signal 2.
- Author
-
Granucci, Francesca, Lutz, Manfred B., and Zanoni, Ivan
- Subjects
DENDRITIC cells ,IMMUNITY ,ANTIGEN presenting cells ,CELLULAR immunity ,CELL communication - Abstract
The article offers the author's opinion on the study on dendritic cells conducted by R. M. Steinman and Z. A. Cohn, who both describe these cells as cells which provide efficient antigen-presenting cells capacity. The author states that this study is significant in determining the role of DCs in activating adaptive immunity and controlling adaptive anti-self reactions. The article also discusses the two major classes of DCs, which are classical or conventional and plasmacytoid DCs (pDCs).
- Published
- 2014
- Full Text
- View/download PDF
50. The nature of activatory and tolerogenic dendritic cell-derived signal 2.
- Author
-
Granucci, Francesca, Lutz, Manfred B., and Zanoni, Ivan
- Subjects
DENDRITIC cells ,NATURAL immunity ,IMMUNE system ,CELL nuclei - Abstract
The authors discuss the characteristic of activatory and tolerogenic dendritic cell-derived signal 2. They cite Charles Janeway who proposed the innate immune recognition theory. which he hypothesized the existence of innate receptors that could alert the immune system to the presence of a pathogen. The authors mention that dendritic cells have been identified as the cells of the innate immune system that transduce signals to the nucleus.
- Published
- 2013
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