Migratory dermal gamma delta T cells determine the balance between lung immunity and tissue damage during Nippostrongylus brasiliensis infection
Many helminth parasites migrate through multiple host organs during infection but how immune responses are relayed across these tissues is still poorly understood. To investigate the cellular and molecular aspects of inter-tissue communication during infection we established a percutaneous infection model with the tissue-migrating nematode Nippostrongylus brasiliensis. High-dimension profiling of the initial cutaneous immune response revealed that dermal {gamma}{delta} T cells become activated via an IL-1R-dependent mechanism, engage cell motility-associated transcriptional pathways and leave the skin after parasite invasion. Chemical and genetic inhibition of leukocyte migration prevents the accumulation of IL-17-producing {gamma}{delta} T cells in the lungs. Notably, bypassing the skin phase of infection, and therefore preventing dermal {gamma}{delta} T cell migration, dampens the increase in early IL-17 production in the lungs, and, instead, leads to enhanced IFN-{gamma} responses together with increased lung damage. Collectively, our data highlights a critical skin-lung axis regulating host-parasite interactions and safeguarding lung health.