Transcriptional remodeling patterns in murine dendritic cells infected with Paracoccidioides brasiliensis: more is not necessarily better

University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Laboratory of Molecular Biology of Pathogenic Fungi. Brasília, DF, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Laboratory of Molecular Biology of Pathogenic Fungi. Brasília, DF, Brazil / University of Brasília. Medical School. Molecular Pathology Post-Graduation Program. Brasília, DF, Brazil.
University of Brasília. Faculty of Ceilândia. Brasília, DF, Brazil.
Harvard Medical School. Beth Israel Deaconess Medical Center. Department of Medicine. Division of Allergy and Inflammation. Boston, MA, United States.
Fundação Oswaldo Cruz. Fiocruz Brasília. Brasília, DF, Brasil.
Federal University of Mato Grosso do Sul. Faculty of Computing. Campo Grande, MS, Brazil.
Washington University School of Medicine. Department of Molecular Microbiology. St. Louis, MO, United States.
Federal University of Mato Grosso do Sul. Faculty of Computing. Campo Grande, MS, Brazil.
University of Brasília. Department of Computer Science. Brasília, DF, Brazil.
University of Brasília. Faculty of Medicine. Brasília, DF, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Laboratory of Applied Immunology. Brasília, DF, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Laboratory of Molecular Biology of Pathogenic Fungi. Brasília, DF, Brazil / University of Brasília. Faculty of Ceilândia. Brasília, DF, Brazil.
University of Brasília. Institute of Biological Sciences. Department of Cell Biology. Laboratory of Molecular Biology of Pathogenic Fungi. Brasília, DF, Brazil / University of Brasília. Medical School. Molecular Pathology Post-Graduation Program. Brasília, DF, Brazil.

Abstract

Most people infected with the fungus Paracoccidioides spp. do not get sick, but approximately 5% develop paracoccidioidomycosis. Understanding how host immunity determinants influence disease development could lead to novel preventative or therapeutic strategies; hence, we used two mouse strains that are resistant (A/J) or susceptible (B10.A) to P. brasiliensis to study how dendritic cells (DCs) respond to the infection. RNA sequencing analysis showed that the susceptible strain DCs remodeled their transcriptomes much more intensely than those from the resistant strain, agreeing with a previous model of more intense innate immunity response in the susceptible strain. Contrastingly, these cells also repress genes/processes involved in antigen processing and presentation, such as lysosomal activity and autophagy. After the interaction with P. brasiliensis, both DCs and macrophages from the susceptible mouse reduced the autophagy marker LC3-II recruitment to the fungal phagosome compared to the resistant strain cells, confirming this pathway’s repression. These results suggest that impairment in antigen processing and presentation processes might be partially responsible for the inefficient activation of the adaptive immune response in this model.

Keywords

Paracoccidioides brasiliensis
Fungal innate immunity
Dendritic cells
Resistance
Susceptibility
A/J and B10, A mouse strains
Autophagy

DeCS

Paracoccidioides
Imunidade Inata
Fungos
Células Dendríticas
Autofagia

Publisher

MDPI

Citation

DE-SOUZA-SILVA, Calliandra M. et al. Transcriptional remodeling patterns in murine dendritic cells infected with Paracoccidioides brasiliensis: more is not necessarily better. Journal of Fungi, [s. l.], v. 6, n. 4, 311, 2020.

DOI

10.3390/jof6040311

ISSN

2309-608X

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/51068

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Open access

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