Institut National de la Recherche Scientifique (INRS)-Centre Armand-Frappier Santé Biotechnologie (CAFSB), Laval, Québec, Canada.
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Infect Immun. 2024 Nov 12;92(11):e0030924. doi: 10.1128/iai.00309-24. Epub 2024 Oct 22.
CXCL16 is a multifaceted chemokine expressed by macrophages and other immune cells in response to viral and bacterial pathogens. However, few studies have investigated its role in parasitic infections. The obligate intracellular parasite () is the causative agent of toxoplasmosis, an infection with potentially deleterious consequences in immunocompromised individuals and the developing fetus of acutely infected pregnant women. Chemokines are critical mediators of host defense and, as such, dysregulation of their expression is a subversion strategy often employed by the parasite to ensure its survival. Herein, we report that types I and II strains upregulated the expression of both transmembrane and soluble forms of CXCL16 in infected bone marrow-derived macrophages (BMDM). Exposure to soluble antigens (STAg) and to excreted-secreted proteins (TgESP) led to the induction of CXCL16. mRNA abundance and CXCL16 protein levels increased in a time-dependent manner upon infection. Importantly, conditioned medium (CM) collected from -infected wild-type (WT) macrophage cultures promoted the migration of RAW264.7 cells expressing CXCR6, the cognate receptor of CXCL16, an effect that was significantly reduced by a neutralizing anti-CXCL16 antibody or use of CM from CXCL16 knockout (KO) macrophages. Lastly, -driven CXCL16 expression appeared to modulate cytokine-induced (IL-4 + IL-13) alternative macrophage activation and M2 phenotypic marker expression. Further investigation is required to determine whether this chemokine contributes to the pathogenesis of toxoplasmosis and to elucidate the underlying molecular mechanisms.
趋化因子 CXCL16 是一种多功能趋化因子,可被巨噬细胞和其他免疫细胞在响应病毒和细菌病原体时表达。然而,很少有研究调查其在寄生虫感染中的作用。专性细胞内寄生虫 ()是弓形虫病的病原体,对于免疫功能低下的个体和急性感染孕妇的胎儿,这种感染具有潜在的有害后果。趋化因子是宿主防御的关键介质,因此,其表达的失调是寄生虫经常采用的颠覆策略,以确保其生存。在此,我们报告 I 型和 II 型 株在感染的骨髓来源巨噬细胞(BMDM)中上调了跨膜和可溶性形式的 CXCL16 的表达。暴露于可溶性 抗原(STAg)和分泌的蛋白质(TgESP)导致 CXCL16 的诱导。在 感染后,CXCL16 的 mRNA 丰度和蛋白水平呈时间依赖性增加。重要的是,从 -感染的野生型(WT)巨噬细胞培养物收集的条件培养基(CM)促进了表达 CXCR6 的 RAW264.7 细胞的迁移,CXCL16 的中和抗体或来自 CXCL16 敲除(KO)巨噬细胞的 CM 显著降低了这种迁移作用。最后,-驱动的 CXCL16 表达似乎调节了细胞因子诱导的(IL-4 + IL-13)替代型巨噬细胞激活和 M2 表型标志物的表达。需要进一步研究以确定这种趋化因子是否有助于弓形虫病的发病机制,并阐明潜在的分子机制。