Disregulation of inflammasome' activation in neutrophil and endothelium in response to SARS-Cov-2 and contribution to severe COVID-19

• Grant number: 20/15323-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2021
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Alessandra Pontillo
• Grantee: Vinícius Nunes Cordeiro Leal
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 21/13049-4 - Molecular mechanisms involved in NLRP3 inflammasome regulation in neutrophils, BE.EP.PD

Abstract

The COVID 19 pandemic is caused by the emerging virus SARS-COV-2 and is responsible for more than 1 million deaths worldwide. The immunopathology of COVID-19 is characterized by a systemic inflammation with significant hematological changes such as neutrophilia and lymphopenia and an exacerbated production of inflammatory cytokines responsible for a viral sepsis in the most severe cases of the disease. IL 1² and IL 18 stand out among the cytokines markedly deregulated during the infection by SARS-COV-2 and both are produced with inflammasome activation The inflammasome is a multiprotein complex activated in response to several PAMPs and DAMPs pathogen and damage associated molecular pattern which are recognized by different cytosolic receptors as NLRP3 the most well known and studied. In the context of SARS COV 2 infection, recent data point to a direct NLRP3 activation in macrophages, however little is known about a possible activation of NLRP3 in other cell types such as neutrophils or endothelial cells. Recent studies indicate that both cells are capable of activating the NLRP3 inflammasome and are involved in the pathogenesis of several infectious diseases, inflammatory and coagulopathies similar to COVID-19 manifestations. In this sense, we intend to investigate the profile of activation of NLRP3 inflammasome complex in neutrophils and endothelial cells with a focus on the severity of the disease as well as the role of inflammasome genetics in the interindividual variability of clinical manifestation, enabling not only a better understanding of the disease's immunopathogenesis but also the identification of possible therapeutic targets helping to face the pandemic. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERNANDES, IARA GRIGOLETTO; OLIVEIRA, LUANA DE M.; ANDRADE, MILENA M. DE SOUZA; ALBERCA, RICARDO W.; LIMA, JULIA CATALDO; DE SOUSA, EMANUELLA SARMENTO ALHO; PIETROBON, ANNA JULIA; PEREIRA, NATALLI ZANETE; BRANCO, ANNA CLAUDIA CALVIELLI CASTELO; DUARTE, ALBERTO JOSE DA SILVA; et al. Resveratrol Upregulates Antioxidant Factors Expression and Downmodulates Interferon-Inducible Antiviral Factors in Aging. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 26, n. 5, p. 15-pg., 2025-03-01. (20/15323-3, 19/02679-7, 20/13148-0, 18/18230-6)

LEAL, VINICIUS NUNES CORDEIRO; ROA, MARIELA ESTEFANY GISLANE VERA; CANTONI, JULIA SILVA; DOS REIS, EDIONE CRISTINA; LARA, AMANDA NAZARETH; PONTILLO, ALESSANDRA. Integrated Genetic and Cellular Analysis Reveals NLRP1 Activation in CD4+T Lymphocytes During Chronic HIV Infection. IMMUNOLOGICAL INVESTIGATIONS, v. N/A, p. 20-pg., 2024-11-01. (21/05420-4, 20/15323-3, 19/06363-4, 17/10824-1, 24/09016-1)

MENDONCA, LEONARDO OLIVEIRA; LEAL, VINICIUS N. C.; ROA, MARIELA E. G., V; BARROS, SAMAR FRESCHI; KALIL, JORGE; PONTILLO, ALESSANDRA. Unexplained fever with consumptive syndrome in the elderly: two cases of VEXAS syndrome with inflammasome dysregulation. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, v. 218, n. 2, p. 8-pg., 2024-09-08. (20/15323-3, 21/05420-4)

LEAL, VINICIUS N. C.; BORK, FRANCESCA; TORTOLA, MARIA MATEO; VON GUILLEAUME, JULI-CHRISTIN; GREVE, CARSTEN L.; BUGL, STEFANIE; DANKER, BETTINA; BITTNER, ZSOFIA A.; GRIMBACHER, BODO; PONTILLO, ALESSANDRA; et al. Bruton's tyrosine kinase (BTK) and matrix metalloproteinase-9 (MMP-9) regulate NLRP3 inflammasome-dependent cytokine and neutrophil extracellular trap responses in primary neutrophils. Journal of Allergy and Clinical Immunology, v. 155, n. 2, p. 14-pg., 2025-02-05. (20/15323-3, 21/13049-4)

DUTRA, VALERIA DE FREITAS; CORDEIRO LEAL, VINICIUS NUNES; PONTILLO, ALESSANDRA. The inflammasomes: crosstalk between innate immunity and hematology. Inflammation Research, v. 71, n. 12, p. 14-pg., 2022-10-20. (20/15323-3)