https://orcid.org/0000-0002-1406-4385
![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
Aim: Cryptococcus gattii causes a severe fungal infection with high mortality rate among immunosuppressed and immunocompetent individuals. Due to limitation of current antifungal treatment, new immunotherapeutic approaches are explored. Methods: This study investigated an immunization strategy utilizing heat-inactivated C. gattii with ArtinM as an adjuvant. C57BL/6 mice were intranasally immunized with heat-killed C. gattii and ArtinM was administrated either before immunization or along with HK-C. gattii. Mice were infected with C. gattii and the efficacy of the immunization protocol was evaluated. Results: Mice that received ArtinM exhibited increased levels of IL-10 and relative expression of IL-23 in the lungs, reduced fungal burden and preserved tissue integrity post-infection. Conclusion: Adjuvant ArtinM improved immunization against C. gattii infection in C57BL/6 mice.
Plain language summary
Cryptococcus gattii is a fungus that can make lungs sick. Right now, there are no good treatments for it, so scientists are trying to find new ways to fight it. In a recent study, they tested a type of immunotherapy called ArtinM to see if it could help. When they gave ArtinM to mice, the mice got healthier and had less fungus in their lungs. This means ArtinM might be able to help fight this fungus.
Given the rising incidence of invasive fungal infections (IFIs), immunomodulation has been considered as a new therapeutic strategy.
IgG anti-GXM levels were reduced in the ArtinM adjuvant group on the 14th day post-infection, suggesting a crucial period for C. gattii challenge.
Lungs of mice receiving ArtinM adjuvant displayed elevated IL-10 levels and reduced relative expression of iNOS and IL-23 after C. gattii infection.
ArtinM adjuvant promoted a balanced immune response in lung tissue, characterized by a non-predominant pattern of pro-inflammatory mediators.
Administration of ArtinM adjuvant significantly reduced the fungal burden in the lungs of C57BL/6 mice after immunization, as confirmed by CFU assay and histological analysis.
ArtinM adjuvant administration before immunization prevented tissue damage caused by inflammatory infiltrates in the lung tissue.
The presence of yeast cells, inflammatory infiltrates and tissue damage was reduced in mice receiving ArtinM adjuvant.
summarizes the main outcomes, illustrating distinct treatment groups, pulmonary fungal burden, percentage of mucicarmine-positive lungs staining and key histopathological findings.
Supplemental material
Supplemental data for this article can be accessed at https://doi.org/10.1080/1750743X.2024.2360384
Acknowledgments
We thank PE Vendruscolo, SMO Thomaz and É Vendruscolo for technical support, and JB Pereira for supporting histological processing, cutting and staining.
Author contributions
Conceptualization, PKM Oliveira-Brito and TA da Silva; methodology, PKM Oliveira-Brito, JE Lazo Chica and TA da Silva; validation, PKM Oliveira-Brito, JE Lazo Chica and TA da Silva; formal analysis, PKM Oliveira-Brito, JE Lazo Chica and TA da Silva; investigation, PKM Oliveira-Brito, GY. de Campos, JG Guimarães, MP Machado, LS da Costa, JE Lazo Chica and TA da Silva; resources, TA da Silva; data curation, PKM Oliveira-Brito and TA da Silva; writing—original draft preparation, PKM Oliveira-Brito, MC Roque-Barreira and TA da Silva; writing—review and editing, PKM Oliveira-Brito and TA da Silva; visualization, PKM Oliveira-Brito and TA da Silva; supervision, TA da Silva; project administration, PKM Oliveira-Brito and TA da Silva; funding acquisition, JE Lazo Chica, MC Roque-Barreira and TA da Silva. All authors have read and agreed to the published version of the manuscript.
Financial disclosure
The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the São Paulo Research Foundation (FAPESP) (Grant Nos. 2016/04877-2; 2018/19949-4; 2018/18538-0; 2018/21708-5; 2019/09261-8; 2019/09260-1; 2019/26074-7), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; 431853/2018-5). FINEP - MCTI/FINEP/CT-infra/01/2013. Convênio 04.13.0479.00. Pesquisa biomédica e tecnológica da Universidade Federal do Triângulo Mineiro - UFTM – Institucional (Microscópio de Luz (LMD 6 systems and motorized stage; Leica, Wetzlar, Germany; XYZ module LX; objectives HC PL FL 1.25×/0.04, 10×/0.30, 20×/0.40, 40×/0.60) and a DFC450 C digital camera (Leica)). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Competing interests disclosure
The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
All animal experiments were performed according to the Ethical Principles Guide for the Care and Use of Laboratory Animals adopted by the Brazilian College of Animal Experimentation. The protocols were approved by the Committee on Ethics in Animal Research of Ribeirão Preto Medical School at the University of São Paulo (protocol no. 192/2018).