The lung is an important site for priming CD 4 T cell mediated 2 protective immunity against gastrointestinal helminth parasites . 3 Running title : The lung is an important site for protective immunity against

19 The rodent hookworm Nippostrongylus brasiliensis typically infects its host by 20 penetrating the skin and rapidly migrating to the lungs and gut. Following primary infection, 21 immune competent mice become highly protected from reinfection by N. brasiliensis with the 22 numbers of worms gaining access to the lung and gut being reduced by up to 90%. We used 23 GFP/IL-4 reporter mice and truncated infection studies, to identify both the tissue site and 24 mechanism(s) by which the host protects itself from reinfection with N. brasiliensis. Strikingly, 25 we demonstrate that the lung is an important site for priming immune protection. Furthermore, a 26 lung-initiated CD4 T cell-dependent, IL-4, STAT6-dependent response was sufficient for 27 conferring protection against reinfection. In conclusion, vaccination strategies which seek to 28 break the cycle of reinfection and egg production by helminths such as hookworm, can include 29 strategies which directly stimulate Th2 responses in the lung. 30 31 on O cber 4, 2017 by gest http/iai.asm .rg/ D ow nladed fom