Nippostrongylus brasiliensis: cytokine responses and nematode expulsion in normal and IL-4-deficient mice.
Infection with the nematode, Nippostrongylus brasiliensis, results in a Th2-dominated immune response. We describe the dynamics of this response in both local and systemic environments. Th2-type responses were evident first in the mesenteric lymph node, with parasite antigen-specific proliferation and IL-4/IL-5 release peaking at Days 7-9 postinfection, shortly before expulsion of the adult worms from the gut. IFN-gamma responses were not observed in the mesenteric lymph node. Responses in the spleen generally followed those in the mesenteric lymph nodes by 2-3 days and showed a greater degree of Th1-type cytokine production. N. brasiliensis was shown to be a powerful inducer of IL-4 responses with as few as six infective N. brasiliensis larvae eliciting IL-4 production in the mesenteric lymph node, but only high doses of larvae (600) elicited IL-4 secretion in the spleen. Similar levels of IL-4 production by lymph node cells stimulated with Con A or parasite antigen postinfection indicated the extent of polyclonal Th2 stimulation by this parasite. Infection of IL-4-deficient mice showed that despite the absence of IL-4-dependent Th2 responses, these mice were able to curtail egg production and expel adult N. brasiliensis in a time frame similar to that of fully immunocompetent animals. These results emphasize the magnitude of the Th2 response to N. brasiliensis and also show that IL-4 is not a prerequisite for the development of immunity to N. brasiliensis.
Wellcome Research Centre for Parasitic Infections, Department of Biology, Imperial College of Science, Technology and Medicine, London, United Kingdom.
R A
RA
Lawrence
C A
CA
Gray
J
J
Osborne
R M
RM
Maizels
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D005243:Feces / Q000469:parasitology; D005260:Female; D007121:Immunocompetence; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency*; D015848:Interleukin-5 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D008297:Male; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus / Q000276:immunology* / Q000502:physiology; D010058:Oviposition; D010270:Parasite Egg Count; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology
D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma