The lung is an important site for priming CD4 T-cell-mediated protective immunity against gastrointestinal helminth parasites.
The rodent hookworm Nippostrongylus brasiliensis typically infects its host by penetrating the skin and rapidly migrating to the lungs and gut. Following primary infection, immunocompetent mice become highly protected from reinfection with N. brasiliensis, with the numbers of worms gaining access to the lungs and gut being reduced by up to 90%. We used green fluorescent protein/interleukin-4 (IL-4) reporter mice and truncated infection studies to identify both the tissue site and mechanism(s) by which the host protects itself from reinfection with N. brasiliensis. Strikingly, we demonstrated that the lung is an important site for priming immune protection. Furthermore, a lung-initiated, CD4 T-cell-dependent, and IL-4- and STAT6-dependent response was sufficient to confer protection against reinfection. In conclusion, vaccination strategies which seek to break the cycle of reinfection and egg production by helminths such as hookworms can include strategies which directly stimulate Th2 responses in the lung.
Harvie
Marina
M
Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand.
Camberis
Mali
M
Tang
Shiau-Choot
SC
Delahunt
Brett
B
Paul
William
W
Le Gros
Graham
G
D000818:Animals; D000909:Antibodies, Helminth / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009559:Nippostrongylus; D012008:Recurrence; D012867:Skin / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology
D000909:Antibodies, Helminth; D016207:Cytokines