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 immunity is regulated 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, 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. ### Competing Interest Statement The authors have declared no competing interest.