BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

Author(s)

Soeiro-Pereira, Paulo Vitor ^[1] ; Falcai, Angela ^[2] ; Kubo, Christina Arslanian ^[3] ; Antunes, Edson ^[4] ; Condino-Neto, Antonio ^[3]

Affiliation

^[1] Univ Fed Maranhao, Curso Med, Pinheiro, MA - Brazil

^[2] Univ Maranhao, Ctr Ensino, Lab Imunol, Sao Luis, MA - Brazil

^[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo, SP - Brazil

^[4] Univ Estadual Campinas, Dept Farmacol, Campinas, SP - Brazil

• Document type: Journal article
• Source: Memórias do Instituto Oswaldo Cruz; v. 110, n. 1, p. 75-85, FEB 2015.
• Web of Science Citations: 0

Abstract

In our previous study, we have found that 5-cyclopropyl-2-{[}1-(2-fluoro-benzyl)-1H-pyrazolo{[}3,4-b]pyridine-3 -yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 412272 might occur primarily by the modulation of the host immune response through macrophage activation. (AU)

• FAPESP's process: 12/50962-0 - New perspectives on neutrophil responses to infections: mechanisms involved in induction and generation of NETs in humans
• Grantee: Paulo Vitor Soeiro Pereira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral