CXCR2 deficiency confers impaired neutrophil recruitment and increased susceptibility during Toxoplasma gondii infection
CXCR2 deficiency confers impaired neutrophil recruitment and increased susceptibility during Toxoplasma gondii infection
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DOI：
10.4049/jimmunol.167.11.6503
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发表时间：
2001-12-01
影响因子：
4.4
通讯作者：
Denkers, EY
中科院分区：
文献类型：
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作者：
Del Rio, L;Bennouna, S;Denkers, EY
中性粒细胞迁移到感染部位是宿主对微生物病原体免疫的关键早期步骤，其中趋化因子及其受体发挥着重要作用。在这项工作中，趋化因子受体 CXCR2 表达缺陷的小鼠被弓形虫感染，并监测结果。基因删除的动物表现出完全有缺陷的中性粒细胞募集，这种情况在 4 小时时很明显，并持续至少 36 小时。 Kit(W)/Kit(W-v)动物也表现出多形核白细胞迁移缺陷，表明肥大细胞是驱动反应的趋化因子的来源之一。 CXCR2(-/-) 动物中速殖子感染和复制加速，导致与野生型对照相比在大脑中建立更高的囊肿数量。此外，与受感染的正常动物相比，受感染的基因缺失小鼠的血清和脾细胞IFN-γ水平降低了60-75%，脾细胞TNF-α同样降低了大约50%。这些结果强调了CXCR2在中性粒细胞迁移中的重要作用，这对于弓形虫感染期间感染的早期控制和免疫诱导可能很重要。
Neutrophil migration to the site of infection is a critical early step in host immunity to microbial pathogens, in which chemokines and their receptors play an important role. In this work, mice deficient in expression of the chemokine receptor CXCR2 were infected with Toxoplasma gondii and the outcome was monitored. Gene-deleted animals displayed completely defective neutrophil recruitment, which was apparent at 4 h and sustained for at least 36 h. Kit(W)/Kit(W-v) animals also displayed defective polymorphonuclear leukocyte migration, suggesting mast cells as one source of chemokines driving the response. Tachyzoite infection and replication were accelerated in CXCR2(-/-) animals, resulting in establishment of higher cyst numbers in the brain relative to wild-type controls. Furthermore, serum and spleen cell IFN-gamma levels in infected, gene-deleted mice were reduced 60-75% relative to infected normal animals, and spleen cell TNF-alpha was likewise reduced by similar to 50%. These results highlight an important role for CXCR2 in neutrophil migration, which may be important for early control of infection and induction of immunity during Toxoplasma infection.