Distribution of paracoccin on the surface of Paracoccidioides brasiliensis and interaction with innate immunity cell receptors: role in the acute phase of paracoccidioidomycosis

• Grant number: 14/05359-0
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): June 01, 2014
• Effective date (End): May 31, 2015
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Maria Cristina Roque Antunes Barreira
• Grantee: Aline Ferreira de Oliveira Pereira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/04088-0 - Lectin from pathogens, AP.TEM

Abstract

Our research group has worked on physical and biological characterization of a lectin from P. brasiliensis, called paracoccin, which plays important role in the biology and pathogenicity of the fungus. Previously, it was shown that paracoccin is present on the yeast surface, predominantly in the budding regions (Coltri et al., 2006). Additionally, this lectin has N-acetylglucosaminidase activity, which is important in the cell wall biogenesis of P. brasiliensis (Almeida dos Reis et al., 2009 and 2011). The important role of the lectin in fungal growth was also suggested by the observation that the addition of anti-paracoccin antibodies to the culture medium of P. brasiliensis yeasts inhibits their growth (Ganiko et al., 2007). Furthermore, paracoccin binds to laminin in a dose- dependent manner, an interaction that is inhibited in the presence of specific sugar (GlcNAc), a property that may contribute to the adherence of the fungus to the extracellular matrix and invasion of host tissues. Paracoccin also induces macrophages to produce TNF- ± and high concentrations of NO (Coltri et al., 2006). The present project is based not only on previous studies with paracoccin, but also with other lectins endowed of immunomodulatory activity, which is triggered by the recognition of glycans of cell receptors involved in innate immunity signaling. In this context, Toledo et al. (2009 ) showed that the plant lectinArtin M induces cytokine production by neutrophils triggered by recognition of N-glycans linked to TLR2 and CXCR2, and it is able to modulate the expression of TLR2 on the cell surface. Moreover, Artin M, by interacting with TLR2 N-glycans, acts on macrophages and dendritic cells, inducing the production of IL- 12 ( Coltri et al. , 2008). The lectin activity of MIC1 / 4 complex, from Toxoplasma gondii, has also been characterized by our research group. It has been identified as responsible for the induction of IL -12 production by murine spleen cells (Lawrence et al. , 2006). Thus, this set of data justify the investment of effort in characterizing paracoccin, in terms of its expression and localization in different fungal forms and its interaction with receptors of innate immunity cells, as well as the biological implications of such interaction.

Scientific publications

(4)

(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)

PAIVA ALEGRE-MALLER, ANA CLAUDIA; MENDONCA, FLAVIA COSTA; DA SILVA, THIAGO APARECIDO; OLIVEIRA, ALINE FERREIRA; FREITAS, MATEUS SILVEIRA; HANNA, EBERT SEIXAS; ALMEIDA, IGOR C.; GAY, NICHOLAS J.; ROQUE-BARREIRA, MARIA CRISTINA. Therapeutic Administration of Recombinant Paracoccin Confers Protection against Paracoccidioides brasiliensis Infection: Involvement of TLRs. PLoS Neglected Tropical Diseases, v. 8, n. 12, DEC 2014. (13/14161-6, 12/20809-6, 14/05359-0, 12/09611-0, 10/01112-9)

FERNANDES, FABRICIO F.; OLIVEIRA, ALINE F.; LANDGRAF, TAISE N.; CUNHA, CRISTINA; CARVALHO, AGOSTINHO; VENDRUSCOLO, PATRICIA E.; GONCALES, RELBER A.; ALMEIDA, FAUSTO; DA SILVA, THIAGO A.; RODRIGUES, FERNANDO; et al. Impact of Paracoccin Gene Silencing on Paracoccidioides brasiliensis Virulence. MBIO, v. 8, n. 4, JUL-AUG 2017. (16/00629-4, 14/05359-0, 14/22561-7, 16/04877-2, 12/09611-0, 13/04088-0)

MILANEZ, GUILHERME P.; WERLE, CATIERINE H.; AMORIM, MARIENE R.; RIBEIRO, RAFAEL A.; TIBO, LUIZ H. S.; ROQUE-BARREIRA, MARIA CRISTINA; OLIVEIRA, ALINE F.; BROCCHI, MARCELO. HU-Lacking Mutants of Salmonella enterica Enteritidis Are Highly Attenuated and Can Induce Protection in Murine Model of Infection. FRONTIERS IN MICROBIOLOGY, v. 9, AUG 22 2018. (13/04088-0, 12/05382-6, 14/13412-8, 14/05359-0)

ASSIS-MARQUES, MARIANA APRIGIO; OLIVEIRA, ALINE FERREIRA; RUAS, LUCIANA PEREIRA; DOS REIS, THAILA FERNANDA; ROQUE-BARREIRA, MARIA CRISTINA; RODRIGUES COELHO, PAULO SERGIO. Saccharomyces cerevisiae Expressing Gp43 Protects Mice against Paracoccidioides brasiliensis Infection. PLoS One, v. 10, n. 3, MAR 19 2015. (13/04088-0, 14/05359-0, 06/60642-2)