Migratory dermal γδ T cells determine the balance between lung immunity and tissue damage during helminth 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 immune aspects of intertissue communication during infection, we established a percutaneous infection model with the tissue-migrating nematode Nippostrongylus brasiliensis. Profiling of the initial cutaneous immune response revealed that dermal γδ T cells become activated via an interleukin 1 receptor (IL-1R)-dependent mechanism, engage cell motility-associated transcriptional pathways, and leave the skin after parasite invasion. Inhibition of leukocyte migration prevents the accumulation of IL-17-producing γδ T cells in the lungs. Bypassing the skin phase of infection, and thereby preventing dermal γδ T cell migration, dampens early IL-17 production in the lungs. This, instead, leads to an enhanced interferon-γ (IFN-γ) response together with increased lung damage. Collectively, our data highlight a critical skin-lung axis regulating host-parasite interactions and safeguarding lung health.