Fc epsilonRI-deficient mice infected with Schistosoma mansoni mount normal Th2-type responses while displaying enhanced liver pathology.
The IgE/Fc epsilonRI interaction is postulated to play an important role in resistance to helminths both at the level of anti-parasitic effector cell function and in the initiation of Th2 responses through IL-4 produced by Fc epsilonRI+ non-B, non-T (NBNT) cells. To formally evaluate the role of IgE/Fc epsilonRI signaling in the host response to helminths we studied Schistosoma mansoni infection in Fc epsilonRI knockout (KO) mice. Infected wild-type (wt) and KO animals showed comparable adult worm and tissue egg burdens, arguing against a role for Fc epsilonRI interactions in host resistance. Significantly, NBNT cells from infected KO, in contrast to wt animals, did not secrete IL-4 when stimulated with anti-IgE Ab or soluble parasite Ag. Nevertheless, serum IgE levels and Th2 cytokine production profiles were comparable in both strains of mice, demonstrating that the Ag-dependent stimulation of IL-4 secretion by NBNT cells is not essential for helminth-induced Th2 differentiation. However, when stimulated with low Ag doses, splenocytes from infected Fc epsilonRI-deficient mice produced less IL-4 in vitro than similar cultures from infected wt animals, an effect attributable to their defective NBNT cell function. Moreover, infected KO mice showed enhanced egg granuloma formation and hepatic fibrosis, revealing that the IgE/Fc epsilonRI interaction, while not essential for Th2 response development or resistance to primary infection, plays a significant role in down-regulating host pathology.
Jankovic
D
D
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kullberg
M C
MC
Dombrowicz
D
D
Barbieri
S
S
Caspar
P
P
Wynn
T A
TA
Paul
W E
WE
Cheever
A W
AW
Kinet
J P
JP
Sher
A
A
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis; D008099:Liver / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017455:Receptors, IgE / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D007377:Interleukin-3; D017455:Receptors, IgE; D015847:Interleukin-4