期刊
ADVANCED BIOLOGY
卷 6, 期 3, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adbi.202101078
关键词
chemokine receptor; helminth; innate immunity; monocyte
资金
- National Institutes of Health/NIAID [R01AI153195, R01AI091759]
This study used specific reporter mice to investigate innate cell subsets in lung helminth infection. It found that mice deficient in CX3CR1 were protected from Nippostrongylus infection, with reduced weight loss, lung leukocyte infiltration, and worm burden. Further research showed that CX3CR1 impairs the interaction between monocytes and the helminth.
Many helminth life cycles, including hookworm, involve a mandatory lung phase, where myeloid and granulocyte subsets interact with the helminth and respond to infection-induced lung injury. To evaluate these innate subsets in Nippostrongylus brasiliensis infection, reporter mice for myeloid cells (CX3CR1(GFP)) and granulocytes (PGRP(dsRED)) are employed. Nippostrongylus infection induces lung infiltration of reporter cells, including CX3CR1(+) myeloid cells and PGRP(+) eosinophils. Strikingly, CX3CR1(GFP/GFP) mice, which are deficient in CX3CR1, are protected from Nippostrongylus infection with reduced weight loss, lung leukocyte infiltration, and worm burden compared to CX3CR1(+/+) mice. This protective effect is specific for CX3CR1 as CCR2-deficient mice do not exhibit reduced worm burdens. Nippostrongylus co-culture with lung Ly6C(+) monocytes or CD11c(+) cells demonstrates that CX3CR1(GFP/GFP) monocytes secrete more pro-inflammatory cytokines and actively bind the parasites causing reduced motility. RNA sequencing of Ly6C(+) or CD11c(+) cells shows Nippostrongylus-induced gene expression changes, particularly in monocytes, associated with inflammation, chemotaxis, and extracellular matrix remodeling pathways. Analysis reveals cytotoxic and adhesion molecules as potential effectors against the parasite, such as Gzma and Gzmb, which are elevated in CX3CR1(GFP/GFP) monocytes. These studies validate a dual innate cell reporter for lung helminth infection and demonstrate that CX3CR1 impairs monocyte-helminth interaction.
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