Valeria Fumagalli
A5036387699- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- Hepatitis B Virus Studies
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- Long-Term Effects of COVID-19
- T-cell and B-cell Immunology
- Liver Disease Diagnosis and Treatment
- Hepatitis C virus research
- Platelet Disorders and Treatments
- Bacterial Infections and Vaccines
- Immune cells in cancer
- Viral gastroenteritis research and epidemiology
- CAR-T cell therapy research
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- Lymphatic System and Diseases
- Hematopoietic Stem Cell Transplantation
- Influenza Virus Research Studies
- RNA Interference and Gene Delivery
- Liver physiology and pathology
- RNA regulation and disease
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Vita-Salute San Raffaele University
2017-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2017-2024
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2017-2024
University of Milano-Bicocca
2015
Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive recognizing hepatocellular driven into state immune dysfunction, identify subset (referred as KC2)...
The development of a tractable small animal model faithfully reproducing human coronavirus disease 2019 pathogenesis would arguably meet pressing need in biomedical research. Thus far, most investigators have used transgenic mice expressing the ACE2 epithelial cells (K18-hACE2 mice) that are intranasally instilled with liquid severe acute respiratory syndrome 2 (SARS-CoV-2) suspension under deep anesthesia. Unfortunately, this experimental approach results disproportionate high central...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus responsible for disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 was reported to alter several cellular pathways, its impact on DNA integrity and mechanisms involved remain unknown. Here we show that causes damage elicits an altered response. Mechanistically, proteins ORF6 NSP13 cause degradation of response kinase CHK1 through proteasome autophagy, respectively. loss leads deoxynucleoside triphosphate (dNTP)...
Abstract Vaccines have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality, yet emerging variants challenge their effectiveness. The prevailing approach to updating vaccines targets the antibody response, operating under presumption that it is primary defense mechanism following vaccination or infection. This perspective, however, can overlook role of T cells, particularly when levels are low absent. Here we show, through studies in mouse models...
Abstract Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS‐CoV‐2 pandemic. Nirmatrelvir—an orally available inhibitor 3‐chymotrypsin‐like cysteine protease—has been shown reduce risk progression severe COVID‐19. However, impact nirmatrelvir treatment on development SARS‐CoV‐2‐specific adaptive immune responses is unknown. Here, by using mouse models infection, we show that administration blunts antibody and T cell responses. Accordingly, upon...
CD8 + T cells are key antiviral effectors against hepatitis B virus (HBV), yet their number and function can be compromised in chronic infections. Preclinical HBV models displaying cell dysfunction showed that interleukin-2 (IL-2)–based treatment, unlike programmed death ligand 1 (PD-L1) checkpoint blockade, could reverse this defect, suggesting its therapeutic potential HBV. However, IL-2’s effectiveness is hindered by pleiotropic nature, because receptor found on various immune cells,...
Reversing CD8+ T cell dysfunction is crucial in treating chronic hepatitis B virus (HBV) infection, yet specific molecular targets remain unclear. Our study analyzed co-signaling receptors during hepatocellular priming and traced the trajectory fate of dysfunctional HBV-specific cells. Early on, these cells upregulate PD-1, CTLA-4, LAG-3, OX40, 4-1BB, ICOS. While blocking co-inhibitory had minimal effect, activating 4-1BB OX40 converted them into antiviral effectors. Prolonged stimulation...
Group 1 innate lymphoid cells (ILCs), which comprise both natural killer (NK) and ILC1s, are important effectors that can also positively negatively influence adaptive immune responses. The latter function is generally ascribed to the ability of NK recognize kill activated T cells. Here, we used multiphoton intravital microscopy in mouse models hepatitis B study intrahepatic behavior group ILCs their cross-talk with virus (HBV)–specific CD8 + We found hepatocellular antigen recognition by...
The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological associated with successful containment in upper airways remains unclear. Here, we combine a multi-omics approach longitudinal sampling reveal temporally resolved signatures non-pneumonic ambulatory infected patients associate specific trajectories airway containment. We see distinct systemic rather than local state containment,...
Abstract Platelet homeostasis is essential for vascular integrity and immune defence 1,2 . Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, cellular molecular mechanisms required to constantly replenish pool MKs their progenitor cells (megakaryopoiesis) remains unclear 3,4 Here we use intravital imaging track dynamics megakaryopoiesis over days. We identify plasmacytoid dendritic (pDCs) as homeostatic sensors that...
Background & AimsLiver diseases resulting from chronic hepatitis B virus (HBV) infection are a significant cause of morbidity and mortality. Vaccines that elicit T cell responses capable controlling the represent treatment strategy with potential for long-term effects. Here, we evaluated vaccines induce activity type I natural killer (NKT) cells to limit viral replication license stimulation conventional antiviral cells.MethodsVaccines were prepared by conjugating peptide epitopes an NKT...
Antibody-mediated clearance of hepatitis B surface antigen (HBsAg) from the circulation chronically infected patients (i.e., seroconversion) is usually associated with increased HBV-specific T cell responsiveness. However, a causative link between serum HBsAg levels and impairment intrahepatic CD8+ cells has not been established. Here we addressed this issue by using HBV replication-competent transgenic mice that are depleted circulating HBsAg, via either spontaneous seroconversion or...
The vaccination campaign against SARS-CoV-2 relies on the world-wide availability of effective vaccines, with a potential need 20 billion vaccine doses to fully vaccinate world population. To reach this goal, manufacturing and logistic processes should be affordable all countries, irrespective economical climatic conditions. Outer membrane vesicles (OMVs) are bacterial-derived that can engineered incorporate heterologous antigens. Given inherent adjuvanticity, such modified OMVs used as...
Here, we provide detailed protocols for the isolation of mouse Kupffer cells - liver-resident macrophages phenotypic (e.g., via flow cytometry, mass or RNA-sequencing) analyses functional experiments involving cell culture. The procedures presented can be adapted other hepatic populations. For complete details on use and execution this protocol, please refer to De Simone et al. (2021).
The vaccination campaign against SARS-CoV-2 relies on the world-wide availability of effective vaccines, with a potential need 20 billion vaccine doses to fully vaccinate world population. To reach this goal, manufacturing and logistic processes should be affordable all countries, irrespectively economical climatic conditions. Outer membrane vesicles (OMV) are bacterial-derived that can engineered incorporate heterologous antigens. Given inherent adjuvanticity, such modified OMV used as...
Innate immune responses to coronavirus infections are highly cell specific. Tissue-resident macrophages, which infected by severe acute respiratory syndrome 2 (SARS-CoV-2) in patients but inconsistently vitro, exert critical conflicting effects secreting both antiviral type I interferons (IFNs) and tissue-damaging inflammatory cytokines. Steroids, the only class of host-targeting drugs approved for treatment disease 2019 (COVID-19), indiscriminately suppress responses, possibly impairing...
Abstract T DC are hematopoietic cells that combine dendritic cell (DC) and conventional T‐cell markers functional properties. They were identified in secondary lymphoid organs (SLOs) of naïve mice as expressing CD11c, major histocompatibility molecules (MHC)‐II, the receptor (TCR). Despite thorough characterization, a physiological role for remains to be determined. Unfortunately, using CD11c marker has caveat its upregulation on different cells, including upon activation. Here, we took...