The impairment in the NLRP3-induced NO secretion renders astrocytes highly permissive to T. cruzi replication

Author(s)

Pacheco, Aline L. ^{[1, 2]} ; Vicentini, Gabriella ^{[1, 2]} ; Matteucci, Kely C. ^{[1, 2]} ; Ribeiro, Rafaela Rosa ^[3] ; Weinlich, Ricardo ^[3] ; Bortoluci, Karina R. ^{[1, 2]}

Affiliation

^[1] Univ Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Ctr Terapia Celular & Mol CTC Mol, Sao Paulo - Brazil

^[3] Hosp Israelita Albert Einstein, Inst Ensino & Pesquisa, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Leukocyte Biology; v. 106, n. 1, p. 201-207, JUL 2019.
• Web of Science Citations: 0

Abstract

Trypanossoma cruzi (T. cruzi), the causative protozoan of Chagas disease (CD) invades many cell types, including central nervous system (CNS) cells triggering local lesions and neurological impact. Previous work from our group described NLRP3 inflammasomes as central effectors for the parasite control by macrophages. Recent evidences demonstrate that NLRP3 can be activated in CNS cells with controversial consequences to the control of infections and inflammatory pathologies. However, the relative contribution of NLRP3 in different cell types remains to be elucidated. In this article, we described an effector response mediated by NLRP3 that works on microglia but not on astrocytes to control T. cruzi infection. Despite T. cruzi ability to invade astrocytes and microglia, astrocytes were clearly more permissive to parasite replication. Moreover, the absence of NLRP3 renders microglia but not astrocytes more permissive to T. cruzi replication. In fact, microglia but not astrocytes were able to secrete NLRP3-dependent IL-1 beta and NO in response to T. cruzi. Importantly, the pharmacological inhibition of iNOS with aminoguanidine resulted in a significant increase in the numbers of amastigotes found in microglia from wild-type but not from NLRP3(-/-) mice, indicating the importance of NLRP3-mediated NO secretion to the infection control by these cells. Taken together, our findings revealed that T. cruzi differentially activates NLRP3 inflammasomes in astrocytes and microglia and established a role for these platforms in the control of a protozoan infection by glial cells from CNS. (AU)

• FAPESP's process: 17/25942-0 - Cross talk between RIP3K and NLRP3 during T. cruzi infection
• Grantee: Karina Ramalho Bortoluci
• Support Opportunities: Regular Research Grants