Adjuvant Curdlan Contributes to Immunization against Cryptococcus gattii Infection in a Mouse Strain-Specific Manner

Author(s)

Martins Oliveira-Brito, Patricia Kellen ; de Campos, Gabriela Yamazaki ; Guimaraes, Julia Garcia ; da Costa, Leticia Serafim ; de Moura, Edanielle Silva ; Lazo-Chica, Javier Emilio ; Roque-Barreira, Maria Cristina ; da Silva, Thiago Aparecido

• Document type: Journal article
• Source: VACCINES; v. 10, n. 4, p. 26-pg., 2022-04-01.

Abstract

The low efficacy and side effects associated with antifungal agents have highlighted the importance of developing immunotherapeutic approaches to treat Cryptococcus gattii infection. We developed an immunization strategy that uses selective Dectin-1 agonist as an adjuvant. BALB/c or C57BL/6 mice received curdlan or beta-glucan peptide (BGP) before immunization with heat-killed C. gattii, and the mice were infected with viable C. gattii on day 14 post immunization and euthanized 14 days after infection. Adjuvant curdlan restored pulmonary tumor necrosis factor-alpha (TNF alpha) levels, as induced by immunization with heat-killed C. gattii. The average area and relative frequency of C. gattii titan cells in the lungs of curdlan-treated BALB/c mice were reduced. However, this did not reduce the pulmonary fungal burden or decrease the i0,nflammatory infiltrate in the pulmonary parenchyma of BALB/c mice. Conversely, adjuvant curdlan induced high levels of interferon-gamma (IFN-gamma) and interleukin (IL)-10 and decreased the C. gattii burden in the lungs of C57BL/6 mice, which was not replicated in beta-glucan peptide-treated mice. The adjuvant curdlan favors the control of C. gattii infection depending on the immune response profile of the mouse strain. This study will have implications for developing new immunotherapeutic approaches to treat C. gattii infection. (AU)

• FAPESP's process: 19/13979-1 - Effect of ArtinM administration, associated with antifungals drugs, on the course of Cryptococcus neoformans infection
• Grantee: Edanielle Silva de Moura
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/09261-8 - Immunotherapy against experimental cryptococcosis: a strategy of vaccination with TLR2 agonists as immunostimulating agents
• Grantee: Júlia Garcia Guimarães
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/18538-0 - Bioengineered of T- and NK-cells by CAR against invasive fungal infections
• Grantee: Thiago Aparecido da Silva
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/09260-1 - Dectin-1 ligands as immunostimulant agents in a vaccination strategy against experimental cryptococcosis
• Grantee: Letícia Serafim da Costa
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/19949-4 - Immunotherapy against experimental Cryptococcosis: a vaccine strategy associated with immunostimulators that recognize carbohydrate
• Grantee: Patrícia Kellen Martins Oliveira Brito
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/04877-2 - Design of new therapeutic strategies, based on the carbohydrate recognition, against cryptococcosis
• Grantee: Thiago Aparecido da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/21708-5 - Application of immunomoduladors, by carbohydrate recognition, as therapeutic agents: mechanism of action to immunotherapy
• Grantee: Maria Cristina Roque Antunes Barreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/26074-7 - Bioengineered of T- and NK-cells by CAR against invasive fungal infections
• Grantee: Thiago Aparecido da Silva
• Support Opportunities: Scholarships in Brazil - Young Researchers