Effect of plant lectins in the macrophages polarization during Cryptococcus gattii infection

• Grant number: 16/17037-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2016
• End date: October 31, 2017
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Thiago Aparecido da Silva
• Grantee: Raquel Amorim Oliveira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Lectins show several biological activities through recognition of mono- or oligosaccharides in a specific and reversible manner. Some plant lectins act on innate and/or adaptive immune cells. In this context, toll-like receptors (TLRs) are recognized by lectins, which can activate antigen presenting cells (APCs). Thus, acting as TLRs agonists, lectins can induce the M1 or M2 polarization. The M1 polarization show higher microbicidal activity favoring a response against intracellular pathogens, and M2 polarization is related to anti-inflammatory profile. Our group has demonstrated that the ArtinM- and Paracoccin-interaction with TLR-N-glycans induces the M1 polarization. Then, we propose to investigate the effect of diverse plant lectins in macrophage polarization. Moreover, we intend to evaluate the effector activity of macrophages stimulated with plants lectins against Cryptococcus gattii infection. We known that C. gattii spore or yeast inhalation promote the cryptococcosis, which affect the lungs of immunocompetent individuals. The M1 macrophages play a role in effector immune response against C.gattii, then our aim is evaluate the immunomodulatory activity of the plant lectins (PHA-E, PHA-L, ConA, ArtinM, Jacalina, UEA, WGA, PNA, ML-1 and Morniga M) on in vitro and in vivo macrophage polarization and repolarization. For this, we propose to quantify the inflammatory mediators production and the relative expression of classic markers to M1 (iNOs) and M2 (Arginase, Fizz, YM-1) cells, after stimulation in vitro and in vivo with lectins. Furthermore, to evaluate the lectin capacity to induce the repolarization for M1 or M2 cells, the cells previously polarized will be incubated with lectins. After, M1 cells induced by lectins will use to evaluate the functional activity, by phagocytosis and killing assay, after infection in vitro with C. gattii. Then, our proposal is associate the importance of macrophage polarization by carbohydrate recognition in TLRs, and also opens new perspectives for studies that relate the modulation of innate immune response against the C. gattii infection.

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)

DE CAMPOS, GABRIELA YAMAZAKI; OLIVEIRA, RAQUEL AMORIM; MARTINS OLIVEIRA-BRITO, PATRICIA KELLEN; ROQUE-BARREIRA, MARIA CRISTINA; DA SILVA, THIAGO APARECIDO. Pro-inflammatory response ensured by LPS and Pam3CSK4 in RAW 264.7 cells did not improve a fungistatic effect on Cryptococcus gattii infection. PeerJ, v. 8, NOV 25 2020. (16/17037-2, 18/21708-5, 18/18538-0, 18/19949-4)