Fc epsilonRI-deficient mice infected with Schistosoma mansoni mount normal Th2-type responses while displaying enhanced liver pathology.

Abstract

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.

A Co-Expressed Natural Antisense RNA FCER1A -AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα

“…S1D and E). This is similar to Th2 responses in S. mansoni infection ( 24 ). The mechanisms underlying the survival advantages provided by FcεRIα await further exploration.…”

“…FcεRIα produces beneficial effects in defense and immunopathology against several types of parasite infections, including Schistosoma mansoni ( 24 ) and Haemaphysalis longicornis ticks ( 25 , 26 ), etc. Lack of FcεRIα causes increased skin penetration by ticks and worsened liver pathologies in animals infected with S. mansoni .…”

Neonatal Exposure to Idiotype InducesSchistosoma mansoniEgg Antigen-Specific Cellular and Humoral Immune Responses

“…It may be possible that IgG2a bound to Fc␥RI or Id/anti-Id immune complexes bound to Fc␥RIII could effect specific immunoregulation by signals delivered through these receptors. This group has also demonstrated a role for Fc⑀RI, the high-affinity receptor for IgE, in immunoregulation of schistosomiasis immunopathology (56). However, although there is IgE in the sera of 8-wk-infected MSS and HSS mice, we have been unable to detect IgE in Id preparations from these animals (data not shown).…”

Tolerization of Mice toSchistosoma mansoniEgg Antigens Causes Elevated Type 1 and Diminished Type 2 Cytokine Responses and Increased Mortality in Acute Infection

“…However, it is relevant that in a separate study in a different B cell-deficient mouse (J H locus deleted) there was a type 1 cytokine-dominated response during acute schistosome infection with normal granulomatous responses (51). Jankovic and colleagues suggest that as FcR-deficient mice also have similar liver pathology as MT mice the role of Ab in regulating the granulomatous response to schistosome eggs is via Ab directly stimulating the production of anti-inflammatory mediators from FcR ϩ cells (50,52).…”