Role of P2X7 receptor on parenchymal and intravascular CD4 T cell response in a Severe Experimental Tuberculosis model

• Grant number: 19/24700-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: February 01, 2020
• End date: March 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Maria Regina D'Império Lima
• Grantee: Igor Santiago de Carvalho
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/20432-8 - Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis, AP.TEM

Abstract

Tuberculosis remains a major public health problem aggravated by the emergence of multidrug-resistant Mycobacterium tuberculosis (Mtb) strains (MDR-TB). Delay in initiation of treatment, high virulence of the infecting strain, and susceptibility to Tuberculosis contribute to the severity of the disease, which is often associated with a deleterious inflammatory response, leading to pulmonary necrosis. Infection of the pulmonary macrophages by the bacilli and their uncontrolled proliferation within the cells causes necrotic death. The released bacilli can infect new cells and thus initiate a new replication cycle. In addition to the spread of Mtb, Damage-Associated Molecular Patterns (DAMPs) are released. ATP released by dying cells is a danger signal that leads to a proinflammatory response, while adenosine, the degradation product of ATP by CD39 and CD73 ecto-nucleotidases, is immunosuppressive. Extracellular ATP can be recognized by purinergic receptors expressed on immune cells. Little is known about the role of purinergic receptor signaling in the immune response and pathogenesis of Tuberculosis. Recently, we have shown that P2X7 purinergic receptor signaling by ATP contributes to the development of severe forms of the disease resulting from infection with hypervirulent strains. However, it is still unclear whether the P2X7 receptor affects the CD4+ T cell response during Tuberculosis. Therefore, the present project aims to evaluate the role of P2X7 receptor in the activation, differentiation and migration of parenchymal and intravascular CD4+ T cells during Tuberculosis caused by hypervirulent mycobacterial strain. We understand that the study of the receptor may contribute to the understanding of the immune response against Tuberculosis, as well as pave the way for new therapeutic approaches using inhibitors of these receptors as an aid in the treatment of Tuberculosis. (AU)

Scientific publications

(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)

SANTIAGO-CARVALHO, IGOR; DE ALMEIDA-SANTOS, GISLANE; BARBOSA BOMFIM, CAIO CESAR; DE SOUZA, PAULA CAROLINA; SANTOS E SILVA, JUAN CARLO; SILVA DE MELO, BRUNO MARCEL; AMARAL, EDUARDO PINHEIRO; PINHEIRO CIONE, MARCOS VINICIOS; LASUNSKAIA, ELENA; HIRATA, MARIO HIROYUKI; et al. P2x7 Receptor Signaling Blockade Reduces Lung Inflammation and Necrosis During Severe Experimental Tuberculosis. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, MAY 5 2021. (19/24700-8, 19/27139-5, 20/09043-8, 17/11030-9, 15/20432-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CARVALHO, Igor Santiago de. CD4+ T cells participate in the immune response of several lung diseases. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.