Souza Ana Camila Oliveira, Favali Cecília, Soares Naiara Caroline, Tavares Natalia Machado, Jerônimo Márcio Sousa, Veloso Junior Paulo Henrique, Marina Clara Luna, Santos Claire, Brodskyn Cláudia, Bocca Anamelia Lorenzetti
Departamento de Biologia Celular, Universidade de Brasília, Brasília, Brazil.
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.
Front Microbiol. 2019 Oct 30;10:2445. doi: 10.3389/fmicb.2019.02445. eCollection 2019.
The cell wall has a critical role in the host immune response to fungal pathogens. In this study, we investigated the influence of two cell wall fractions of the dimorphic fungi (Pb) in the generation of monocyte-derived dendritic cells (MoDCs). Monocytes were purified from the peripheral blood of healthy donors and cultivated for 7 days in medium supplemented with IL-4 and GM-CSF in the presence of Pb cell wall fractions: the alkali-insoluble F1, constituted by β-1,3-glucans, chitin and proteins, and the alkali-soluble F2, mainly constituted by α-glucan. MoDCs phenotypes were evaluated regarding cell surface expression of CD1a, DC-SIGN, HLA-DR, CD80, and CD83 and production of cytokines. The α-glucan-rich cell wall fraction downregulated the differentiation of CD1a MoDCs, a dendritic cell subset that stimulate Th1 responses. The presence of both cell fractions inhibited DC-SIGN and HLA-DR expression, while the expression of maturation markers was differentially induced in CD1a MoDCs. Differentiation upon F1 and F2 stimulation induced mixed profile of inflammatory cytokines. Altogether, these data demonstrate that Pb cell wall fractions differentially induce a dysregulation in DCs differentiation. Moreover, our results suggest that cell wall α-glucan promote the differentiation of CD1a DCs, potentially favoring Th2 polarization and contributing to pathogen persistence.
细胞壁在宿主对真菌病原体的免疫反应中起着关键作用。在本研究中，我们调查了双态真菌（Pb）的两种细胞壁组分对单核细胞衍生树突状细胞（MoDCs）生成的影响。从健康供体的外周血中纯化单核细胞，并在添加白细胞介素-4和粒细胞-巨噬细胞集落刺激因子的培养基中，于Pb细胞壁组分存在的情况下培养7天：碱不溶性F1，由β-1,3-葡聚糖、几丁质和蛋白质组成；碱溶性F2，主要由α-葡聚糖组成。从细胞表面CD1a、树突状细胞特异性细胞间黏附分子-3抓取非整合素（DC-SIGN）、人白细胞抗原-DR（HLA-DR）、CD80和CD83的表达以及细胞因子的产生方面评估MoDCs的表型。富含α-葡聚糖的细胞壁组分下调了刺激Th1反应的树突状细胞亚群CD1a MoDCs的分化。两种细胞组分的存在均抑制DC-SIGN和HLA-DR的表达，而成熟标志物的表达在CD1a MoDCs中受到不同诱导。F1和F2刺激后的分化诱导了炎性细胞因子的混合谱。总之，这些数据表明Pb细胞壁组分在DCs分化中差异诱导失调。此外，我们的结果表明细胞壁α-葡聚糖促进CD1a DCs的分化，可能有利于Th2极化并导致病原体持续存在。
