Journal
VACCINES
Volume 10, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/vaccines10040620
Keywords
Cryptococcus gattii; immunotherapy; curdlan; beta-glucan peptide; Dectin-1
Categories
Funding
- Sao Paulo Research Foundation (FAPESP) [2016/04877-2, 2018/19949-4, 2018/18538-0, 2018/21708-5, 2019/13979-1, 2019/09261-8, 2019/09260-1, 2019/26074-7]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Amparo a Pesquisa e Assistencia (FAEPA) do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
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This study developed an immunization strategy using a selective Dectin-1 agonist as an adjuvant to treat Cryptococcus gattii infection. The strategy improved immune response and reduced lung infection.
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.
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