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Article ; Online: γδ T Cells in Emerging Viral Infection: An Overview.

Cimini, Eleonora / Agrati, Chiara

2022 Volume 14, Issue 6

Abstract: New emerging viruses belonging to ... ...

Abstract	New emerging viruses belonging to the
MeSH term(s)	Antiviral Agents ; COVID-19 ; Humans ; Immunity, Innate ; Pandemics ; SARS-CoV-2
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2022-05-27
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14061166
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Article: γδ T Cells in Emerging Viral Infection: An Overview

Cimini, Eleonora / Agrati, Chiara

Viruses. 2022 May 27, v. 14, no. 6

2022

Abstract: New emerging viruses belonging to the Coronaviridae, Flaviviridae, and Filoviridae families are serious threats to public health and represent a global concern. The surveillance to monitor the emergence of new viruses and their transmission is an ... ...

Abstract	New emerging viruses belonging to the Coronaviridae, Flaviviridae, and Filoviridae families are serious threats to public health and represent a global concern. The surveillance to monitor the emergence of new viruses and their transmission is an important target for public health authorities. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an excellent example of a pathogen able to cause a pandemic. In a few months, SARS-CoV-2 has spread globally from China, and it has become a world health problem. Gammadelta (γδ) T cell are sentinels of innate immunity and are able to protect the host from viral infections. They enrich many tissues, such as the skin, intestines, and lungs where they can sense and fight the microbes, thus contributing to the protective immune response. γδ T cells perform their direct antiviral activity by cytolytic and non-cytolytic mechanisms against a wide range of viruses, and they are able to orchestrate the cellular interplay between innate and acquired immunity. For their pleiotropic features, γδ T cells have been proposed as a target for immunotherapies in both cancer and viral infections. In this review, we analyzed the role of γδ T cells in emerging viral infections to define the profile of the response and to better depict their role in the host protection.
Keywords	Filoviridae ; Flaviviridae ; Severe acute respiratory syndrome coronavirus 2 ; T-lymphocytes ; adaptive immunity ; antiviral properties ; immune response ; innate immunity ; monitoring ; pandemic ; pathogens ; public health ; China
Language	English
Dates of publication	2022-0527
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14061166
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Article ; Online: SARS-CoV-2 Infection of Airway Epithelium Triggers Pulmonary Endothelial Cell Activation and Senescence Associated with Type I IFN Production.

Bordoni, Veronica / Mariotti, Davide / Matusali, Giulia / Colavita, Francesca / Cimini, Eleonora / Ippolito, Giuseppe / Agrati, Chiara

Cells

2022 Volume 11, Issue 18

Abstract: Airway epithelial cells represent the main target of SARS-CoV-2 replication but several pieces of evidence suggest that endothelial cells (ECs), lining pulmonary blood vessels, are key players in lung injury in COVID-19 patients. Although in vivo ... ...

Abstract	Airway epithelial cells represent the main target of SARS-CoV-2 replication but several pieces of evidence suggest that endothelial cells (ECs), lining pulmonary blood vessels, are key players in lung injury in COVID-19 patients. Although in vivo evidence of SARS-CoV-2 affecting the vascular endothelium exists, in vitro data are limited. In the present study, we set up an organotypic model to dissect the crosstalk between airway epithelium and pulmonary endothelial cells during SARS-CoV-2 infection. We showed that SARS-CoV-2 infected airway epithelium triggers the induction of endothelial adhesion molecules in ECs, suggesting a bystander effect of dangerous soluble signals from the infected epithelium. The endothelial activation was correlated with inflammatory cytokines (IL-1β, IL-6, IL-8) and with the viral replication in the airway epithelium. Interestingly, SARS-CoV-2 infection determined a modulation of endothelial p21, which could be partially reversed by inhibiting IFN-β production from ECs when co-cultured with HAE. Altogether, we demonstrated that SARS-CoV-2 infected epithelium triggers activation/senescence processes in ECs involving type I IFN-β production, suggesting possible antiviral/damage mechanisms occurring in the endothelium.
MeSH term(s)	COVID-19/immunology ; Cellular Senescence ; Endothelial Cells/immunology ; Epithelium ; Humans ; Interferon Type I/immunology ; Interleukin-6 ; Interleukin-8 ; Lung ; SARS-CoV-2
Chemical Substances	Interferon Type I ; Interleukin-6 ; Interleukin-8
Language	English
Publishing date	2022-09-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11182912
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Article ; Online: Emerging viral infections in immunocompromised patients: A great challenge to better define the role of immune response.

Agrati, Chiara / Bartolini, Barbara / Bordoni, Veronica / Locatelli, Franco / Capobianchi, Maria Rosaria / Di Caro, Antonino / Castilletti, Concetta / Ippolito, Giuseppe

Frontiers in immunology

2023 Volume 14, Page(s) 1147871

Abstract: The immune response to invading pathogens is characterized by the rapid establishment of a complex network of cellular interactions and soluble signals. The correct balancing of activating and regulating pathways and tissue-homing signals determines its ... ...

Abstract	The immune response to invading pathogens is characterized by the rapid establishment of a complex network of cellular interactions and soluble signals. The correct balancing of activating and regulating pathways and tissue-homing signals determines its effectiveness and persistence over time. Emerging viral pathogens have always represented a great challenge to the immune system and an often uncontrolled/imbalanced immune response has been described (e.g. cytokine storm, immune paralysis), contributing to the severity of the disease. Several immune biomarkers and cell subsets have been identified as major players in the cascade of events leading to severe diseases, highlighting the rationale for host-directed intervention strategy. There are millions of immunocompromised pediatric and adult patients worldwide (e.g. transplant recipients, hematologic patients, subjects with primary immune-deficiencies), experiencing an impaired immune reactivity, due to diseases and/or to the medical treatments. The reduced immune reactivity could have two paradoxical non-exclusive effects: a weak protective immunity on one hand, and a reduced contribution to immune-mediated pathogenetic processes on the other hand. In these sensitive contexts, the impact of emerging infections represents a still open issue to be explored with several challenges for immunologists, virologists, physicians and epidemiologists. In this review, we will address emerging infections in immunocompromised hosts, to summarize the available data concerning the immune response profile, its influence on the clinical presentation, the possible contribution of persistent viral shedding in generating new viral variants with improved immune escape features, and the key role of vaccination.
MeSH term(s)	Humans ; Child ; Virus Diseases ; Immunocompromised Host ; Immunity
Language	English
Publishing date	2023-03-09
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1147871
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Article ; Online: Brief Report: In cART-Treated HIV-Infected Patients, Immunologic Failure Is Associated With a High Myeloid-Derived Suppressor Cell Frequency.

Grassi, Germana / Notari, Stefania / Cicalini, Stefania / Casetti, Rita / Cimini, Eleonora / Bordoni, Veronica / Gagliardini, Roberta / Mazzotta, Valentina / Antinori, Andrea / Agrati, Chiara / Sacchi, Alessandra

Journal of acquired immune deficiency syndromes (1999)

2024 Volume 95, Issue 2, Page(s) 185–189

Abstract: Background: During HIV infection, effective combined antiretroviral therapy suppresses viral replication and restores the number of circulating CD4+ T cells. However, 15%-30% of treated patients show a discordant response to combined antiretroviral ... ...

Abstract	Background: During HIV infection, effective combined antiretroviral therapy suppresses viral replication and restores the number of circulating CD4+ T cells. However, 15%-30% of treated patients show a discordant response to combined antiretroviral therapy. Myeloid-derived suppressor cells (MDSC) are expanded in HIV+ patients; to better understand the role of MDSC on CD4 T-cell recovery, we evaluated the frequency of MDSC in HIV+ patients under combined antiretroviral therapy and its association with immunologic response. Methods: We enrolled 60 HIV+ patients, including complete responders (R, n = 44), virologic nonresponders (VNR, n = 5), and immunologic nonresponders (INR, n = 11). The frequency of circulating MDSC and the percentage of activated and naïve CD4 T cells were evaluated by flow cytometry. Plasmatic cytokine levels were analyzed by automated ELISA. Results: As previously observed, polymorphonuclear MDSC (PMN-MDSC) frequency was higher in HIV+ patients compared with healthy donors. Furthermore, PMN-MDSC percentage was higher in INR than R patients, and a significant association between MDSC frequency and immunologic failure was confirmed by a receiver operator characteristic analysis. Accordingly, an inverse correlation was found between the percentages of PMN-MDSC and naïve CD4 T cells. A positive correlation was observed between PMN-MDSC frequency and the percentage of human leucocyte antigen locus DR + CD4 T cells and the plasmatic level of IL-1β and IL-8. Conclusion: Our results show that a high frequency of PMN-MDSC persists in INR, possibly because of immune activation, contributing to CD4 T-cell recovery failure. These findings further highlight the detrimental role of MDSC during HIV infection, suggesting these cells as a possible new therapeutic target.
MeSH term(s)	Humans ; Myeloid-Derived Suppressor Cells ; HIV Infections ; CD4-Positive T-Lymphocytes ; Cytokines ; Enzyme-Linked Immunosorbent Assay
Chemical Substances	Cytokines
Language	English
Publishing date	2024-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000003335
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Article ; Online: Correction to: Plasma concentrations of remdesivir metabolite in a critical COVID-19 patient needing continuous venovenous haemodialysis.

Tempestilli, Massimo / Stazi, Giulia Valeria / Maffongelli, Gaetano / Marini, Maria Cristina / Bartoli, Tommaso Ascoli / Ippolito, Giuseppe / Nicastri, Emanuele / Marchioni, Luisa / Agrati, Chiara

European journal of clinical pharmacology

2022 Volume 78, Issue 5, Page(s) 895

Language	English
Publishing date	2022-04-07
Publishing country	Germany
Document type	Published Erratum
ZDB-ID	121960-1
ISSN	1432-1041 ; 0031-6970
ISSN (online)	1432-1041
ISSN	0031-6970
DOI	10.1007/s00228-022-03305-2
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Article ; Online: Venous thromboembolism in people living with HIV infection (PWH).

Agrati, Chiara / Mazzotta, Valentina / Pinnetti, Carmela / Biava, Gianluigi / Bibas, Michele

Translational research : the journal of laboratory and clinical medicine

2020 Volume 227, Page(s) 89–99

Abstract: The risk of venous thromboembolism (VTE) and of recurrent VTE remain elevated in people living with HIV compared to controls still with contemporary antiretroviral therapy (ART). The pathophysiology of VTE in HIV is multi factorial and includes an ... ...

Abstract	The risk of venous thromboembolism (VTE) and of recurrent VTE remain elevated in people living with HIV compared to controls still with contemporary antiretroviral therapy (ART). The pathophysiology of VTE in HIV is multi factorial and includes an interplay among traditional risk factors, HIV-specific factors, behavioral factors, exposure to ART and other therapies, coinfections, and co-morbidities.
MeSH term(s)	Adult ; Anti-HIV Agents/therapeutic use ; Female ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Male ; Middle Aged ; Venous Thromboembolism/complications
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2020-07-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2246684-8
ISSN	1878-1810 ; 1532-6543 ; 1931-5244
ISSN (online)	1878-1810 ; 1532-6543
ISSN	1931-5244
DOI	10.1016/j.trsl.2020.07.007
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Article ; Online: Pharmacokinetics of bictegravir, emtricitabine and tenofovir alafenamide in a gastrectomized patient with HIV.

Tempestilli, Massimo / D'Avolio, Antonio / De Nicolò, Amedeo / Agrati, Chiara / Antinori, Andrea / Cicalini, Stefania

The Journal of antimicrobial chemotherapy

2021 Volume 76, Issue 12, Page(s) 3320–3322

MeSH term(s)	Alanine/therapeutic use ; Amides ; Anti-HIV Agents/therapeutic use ; Emtricitabine/therapeutic use ; HIV Infections/drug therapy ; Heterocyclic Compounds, 3-Ring/therapeutic use ; Humans ; Piperazines ; Pyridones/therapeutic use ; Tenofovir/analogs & derivatives
Chemical Substances	Amides ; Anti-HIV Agents ; Heterocyclic Compounds, 3-Ring ; Piperazines ; Pyridones ; bictegravir (8GB79LOJ07) ; Tenofovir (99YXE507IL) ; tenofovir alafenamide (EL9943AG5J) ; Emtricitabine (G70B4ETF4S) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2021-08-25
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkab319
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Article ; Online: The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review.

Agrati, Chiara / Sacchi, Alessandra / Tartaglia, Eleonora / Vergori, Alessandra / Gagliardini, Roberta / Scarabello, Alessandra / Bibas, Michele

International journal of molecular sciences

2021 Volume 22, Issue 15

Abstract: In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The ... ...

Abstract	In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention.
MeSH term(s)	Blood Coagulation Disorders/blood ; Blood Coagulation Disorders/etiology ; Blood Platelets/metabolism ; COVID-19/complications ; Endothelial Cells/metabolism ; Humans ; Leukocytes/metabolism ; P-Selectin/blood
Chemical Substances	P-Selectin ; SELP protein, human
Language	English
Publishing date	2021-07-26
Publishing country	Switzerland
Document type	Journal Article ; Systematic Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22157942
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Article ; Online: The immune response as a double-edged sword: The lesson learnt during the COVID-19 pandemic.

Agrati, Chiara / Carsetti, Rita / Bordoni, Veronica / Sacchi, Alessandra / Quintarelli, Concetta / Locatelli, Franco / Ippolito, Giuseppe / Capobianchi, Maria R

Immunology

2022 Volume 167, Issue 3, Page(s) 287–302

Abstract: The COVID-19 pandemic has represented an unprecedented challenge for the humanity, and scientists around the world provided a huge effort to elucidate critical aspects in the fight against the pathogen, useful in designing public health strategies, ... ...

Abstract	The COVID-19 pandemic has represented an unprecedented challenge for the humanity, and scientists around the world provided a huge effort to elucidate critical aspects in the fight against the pathogen, useful in designing public health strategies, vaccines and therapeutic approaches. One of the first pieces of evidence characterizing the SARS-CoV-2 infection has been its breadth of clinical presentation, ranging from asymptomatic to severe/deadly disease, and the indication of the key role played by the immune response in influencing disease severity. This review is aimed at summarizing what the SARS-CoV-2 infection taught us about the immune response, highlighting its features of a double-edged sword mediating both protective and pathogenic processes. We will discuss the protective role of soluble and cellular innate immunity and the detrimental power of a hyper-inflammation-shaped immune response, resulting in tissue injury and immunothrombotic events. We will review the importance of B- and T-cell immunity in reducing the clinical severity and their ability to cross-recognize viral variants.
MeSH term(s)	COVID-19 ; Humans ; Immunity ; Inflammation ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2022-09-05
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.13564
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