Division of Biomedical Sciences, School of Medicine, University of California, Riverside, California, USA.
Department of Biological Sciences, California State Polytechnic University, Pomona, California, USA.
Parasite Immunol. 2023 Dec;45(12):e13011. doi: 10.1111/pim.13011. Epub 2023 Sep 30.
The protozoan parasite Toxoplasma gondii infects approximately 2.5 billion people worldwide. Infection induces a rapid dissemination of parasites throughout the body followed by the formation of lifelong cysts within neurons of the host brain. Both stages require a dynamic immune response comprised of both innate and adaptive cells. Neutrophils are a primary responding cell to acute infection and have been observed in the brain during murine chronic infection. Previous studies investigating human neutrophils found that invasion by Toxoplasma tachyzoites inhibits apoptosis of neutrophils, prolonging their survival under inflammatory conditions. Here, we demonstrate the differentiation of two distinct subsets following exposure of human neutrophil-like-cells (HNLC) to Toxoplasma cysts. In vitro stimulation and imaging studies show cyst-specific induction of cytokines and cyst clearance by HNLCs. Further testing demonstrates that aged HNLCs perform less phagocytosis of cysts compared to non-aged HNLCs. In conclusion, this study identifies a novel response of HNLCs to Toxoplasma cysts and may indicate a role for neutrophils in the clearance of cysts during human infection with Toxoplasma.
原生动物寄生虫刚地弓形虫感染全世界约 25 亿人。感染诱导寄生虫在全身迅速传播，随后在宿主大脑神经元内形成终身囊肿。这两个阶段都需要由先天和适应性细胞组成的动态免疫反应。中性粒细胞是急性感染的主要反应细胞，在鼠慢性感染期间观察到在大脑中存在。先前研究人类中性粒细胞的研究发现，刚地弓形虫速殖子的入侵抑制了中性粒细胞的凋亡，在炎症条件下延长了它们的存活时间。在这里，我们展示了人类中性粒细胞样细胞（HNLC）暴露于刚地弓形虫包囊后分化为两个不同的亚群。体外刺激和成像研究表明，包囊特异性诱导 HNLC 细胞因子和包囊清除。进一步的测试表明，与非老化 HNLC 相比，老化的 HNLC 对包囊的吞噬作用较小。总之，这项研究确定了 HNLC 对刚地弓形虫包囊的新反应，这可能表明在人类感染刚地弓形虫期间中性粒细胞在清除包囊方面的作用。
