Effect of ArtinM lectin in the activation of neutrophils by Paracoccidioides brasiliensis

• Grant number: 14/06155-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2014
• Effective date (End): April 30, 2016
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Luciana Pereira Ruas
• Grantee: Livia Moreira Genaro
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Paracoccidioidomycosis (PCM), caused by the fungus Paracoccidioides brasiliensis, is the most prevalent systemic mycosis in South America, including Brazil, Argentina, Colombia, and Venezuela. In Brazil, the disease is the leading cause of death among immunocompetent individuals. The immune response involved in the resistance to P. brasiliensis depends mainly upon a vigorous Th1-based, cellular immune response, with activation of macrophages. Neutrophils are also reported to have a role during P. brasiliensis infection. Neutrophils are able to ingest P. brasiliensis yeast cells, but their fungicidal capacity is reduced. They must be previously activated to be able to kill P. brasiliensis yeast cells. Despite significant developments in P. brasiliensis antifungal chemotherapy, its efficacy remains limited since drug therapy is prolonged and associated with toxic side effects and relapses. Hence, there is a strong need for alternative or complementary to conventional chemotherapy. ArtinM is a lectin from jackfruit seeds (Artocarpus heterophyllus) which modulates immunity during experimental infections with several intracellular pathogens, including P. brasiliensis. Both prophylactic and therapeutic protocols of ArtinM administration to P. brasiliensis infected mice promote a Th1 immune response balanced by IL-10, which reduces the fungal load in organs of the treated mice while maintaining a controlled inflammation at the site of infection. The action of ArtinM comprises several cells of the immune system, including neutrophils. In this project we propose to investigate the effect of ArtinM lectin in human neutrophils cultured in vitro with P. brasiliensis yeasts. For that, we intend to assess cytokine production, expression of chemokine receptors and generation of reactive oxygen species (ROS) by peripheral blood neutrophils during P. brasiliensis in vitro infection. We believe that this study will contribute to a better understanding of the immunopathology of PCM and also to identify new therapeutic strategies. (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)

RUAS, LUCIANA P.; GENARO, LIVIA M.; JUSTO-JUNIOR, AMAURI S.; COSER, LILIAN O.; DE CASTRO, LIVIA F.; TRABASSO, PLINIO; MAMONI, RONEI L.; ROQUE-BARREIRA, MARIA-CRISTINA; BLOTTA, MARIA-HELOISA S. L.. Effect of ArtinM on Human Blood Cells During Infection With Paracoccidioides brasiliensis. FRONTIERS IN MICROBIOLOGY, v. 9, MAY 4 2018. (14/12516-4, 13/24742-6, 14/06155-9)