Recombinant <i>Dirofilaria immitis</i>-Derived Antigen Can Suppress Passive Cutaneous Anaphylaxis Reactions

Abstract

Background: High levels of antigen-nonspecific IgE are produced in animals infected with helminth parasites. Generally, the increase in IgE is thought to exacerbate allergic reactions. However, high levels of antigen-nonspecific IgE may alter some features of anaphylactic reactions. To investigate the molecular mechanisms of antigen-nonspecific IgE production induced during filarial infections, we previously constructed rDiAg (recombinant Dirofilaria immitis-derived antigen) in Escherichia coli. In the present study, we examined the effect of rDiAg on the production of antigen-nonspecific IgE and on allergic cutaneous reactions in rats. Methods: Osmotic pumps filled with 200 µg of rDiAg or with 200 µl of PBS (control) were subcutaneously implanted in Wistar rats, and plasma samples were collected weekly thereafter. IgE levels were determined by ELISA. Homologous passive cutaneous anaphylaxis (PCA) reactions with anti-DNP-As IgE were examined 21 days after implantation. ¹²⁵I-IgE binding assays were examined on peritoneal mast cells from rDiAg-infused rats and control rats. Results: Antigen-nonspecific IgE production was induced in rDiAg-infused rats. PCA reactions were suppressed in rDiAg-infused rats in spite of high levels of IgE and a markedly increased expression of FcΕRI. ¹²⁵I-IgE did not bind to mast cells derived from rDiAg-infused rats, but it bound dose dependently to mast cells derived from control rats. Conclusion: The present data support the hypothesis that antigen-nonspecific IgE might protect against antigen-specific IgE by means of competition for mast cell receptors. rDiAg is an essential factor to induce antigen-nonspecific IgE in helminth infections.

A Factor of Inducing IgE from a Filarial Parasite Is an Agonist of Human CD40

“…Our results were in agreement with the previous report of marked elevation of polyclonal IgE levels in the early phase of Nippostrongylus brasiliensis infections (5). The same phenomenon has also been observed in rats (10).…”

“…Lee et al demonstrated that Ascaris suum pseudocoelomic body fluid contains a B cell mitogen (8) and induces high levels of total circulating IgE (9). We previously purified a factor from D. immitis that induces antigen-nonspecific IgE in mice and rats and named it DiAg (10). DiAg was identical to one already identified as a polyradderprotein, or neutrophil chemotactic factor (DiNCF; GenBank TM accession number D88757) (11).…”

A Factor of Inducing IgE from a Filarial Parasite Prevents Insulin-Dependent Diabetes Mellitus in Nonobese Diabetic Mice

“…We previously purified a factor from Dirofilaria immitis that induces antigennonspecific immunoglobulin E (IgE) in mice and rats (2). We demonstrated that DiAg is an essential factor to induce antigen-nonspecific IgE in helminth infection.…”

“…We demonstrated that DiAg is an essential factor to induce antigen-nonspecific IgE in helminth infection. Recombinant DiAg (rDiAg) is able to suppress passive cutaneous anaphylaxis (2). We concluded that antigennonspecific IgE protect against antigen-specific IgE by means of competition for mast cell receptors.…”

Various Types ofDirofilaria immitisPolyproteins Selectively Induce a Th2-Type Immune Response

“…DiAg monomer, the dominant ES product of the worm, can be divided into two types based on the difference of sequence on C-terminal half. We have previously found that DiAg monomer (either native [including V1 and V2] or recombinant [V1]) has the ability to induce nonspecific IgE synthesis (10,17,18,33,40). However, little is known about biological activities of another monomer (V2) and dimers.…”