de-Souza-Silva Calliandra M, Hurtado Fabián Andrés, Tavares Aldo Henrique, de Oliveira Getúlio P, Raiol Taina, Nishibe Christiane, Agustinho Daniel Paiva, Almeida Nalvo Franco, Walter Maria Emília Machado Telles, Nicola André Moraes, Bocca Anamélia Lorenzetti, Albuquerque Patrícia, Silva-Pereira Ildinete
Laboratory of Molecular Biology of Pathogenic Fungi, Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília, DF 70910-900, Brazil.
Molecular Pathology Post-Graduation Program, University of Brasília Medical School, Brasília, DF 70910-900, Brazil.
J Fungi (Basel). 2020 Nov 24;6(4):311. doi: 10.3390/jof6040311.
Most people infected with the fungus 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 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 , 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.
大多数感染真菌属的人不会生病，但约5%的人会患上副球孢子菌病。了解宿主免疫决定因素如何影响疾病发展可能会带来新的预防或治疗策略；因此，我们使用了对该真菌有抗性（A/J）或易感性（B10.A）的两种小鼠品系，来研究树突状细胞（DCs）对感染的反应。RNA测序分析表明，易感品系的DCs比抗性品系的DCs更强烈地重塑其转录组，这与之前关于易感品系中更强烈的先天免疫反应模型一致。相反，这些细胞也会抑制参与抗原加工和呈递的基因/过程，如溶酶体活性和自噬。与抗性品系细胞相比，与该真菌相互作用后，易感小鼠的DCs和巨噬细胞都减少了自噬标记物LC3-II向真菌吞噬体的募集，证实了该途径的抑制。这些结果表明，抗原加工和呈递过程的受损可能部分导致了该模型中适应性免疫反应的低效激活。
