Galectin and aldolase‐like molecules are responsible for the specific IgE response in humans exposed to Dirofilaria immitis

Abstract

Dirofilaria immitis is the agent of the heartworm disease in canids and felids, and of pulmonary dirofilariosis in man. Like other filariae, D. immitis harbours endosymbion Wolbachia bacteriae. In this work we analyse the response of specific IgE antibodies against both D. immitis antigens and the Wolbachia surface protein (WSP) in two groups of persons living in an area of canine endemia, one presenting high levels of total IgE (group 1) and other with normal levels (group 2). Infections with D. immitis were demonstrated by the presence of specific IgG in 228 individuals(48.8%) of the group 1 and only in one of the group 2. Specific IgE antibody response against D. immitis antigens was detected only in individuals of the group 1. IgE response against WSP was not detected in any group. The IgE response was directed mainly against two molecules of 33 and 42 kDa of the antigenic extract of D. immitis. These molecules were identified by mass spectrometry as a galectin and an aldolase, respectively. Their possible role in the survival mechanisms of the parasite and their contribution to development of allergic reactions in individuals resident in areas with heartworm disease are discussed.

Stage-specific proteomic expression patterns of the human filarial parasiteBrugia malayiand its endosymbiontWolbachia

“…Some of these immunologically relevant proteins have been described previously (23-33) and relate to those molecules that are highly immunogenic in human infections or that have activity on the mammalian host immune response (through mimicry or other mechanisms). These data corroborate a number of previous studies that demonstrate stage-specific expression and/or serologic reactivity of ALT-2 and the larval allergens (in the L3 stage) (34) and BmR1 (35), BmMIF (36), TGF-β homologue (30), SXP-1 (37), galectins (38), and microfilarial sheath proteins (in the microfilarial stage) (39). Particular sets of ECM-associated proteins were common and highly enriched in the both the L3s (SI Appendix, Fig.…”

Identification of Immunodominant Peptides from Gnathostoma binucleatum

“…Using G. spinigerum L3 antigen and the serum of infected patients, Tapchaisri and others 14 identified more than 20 antigenic bands (13-150 kDa), 16 of which were prominent (21,22,24,32,33,34,35,38,42,43,49,94,120,135, and 150 kDa), that were recognized commonly by serum samples from most patients with gnathostomiasis. Proteins with molecular weights 30 kDa cross-reacted with serum samples from patients with other parasitic diseases, and some high molecular weight proteins reacted nonspecifically with serum samples from healthy persons.…”

“…30 Moreover, this molecule was also found in an array of parasitic nematodes such as B. malayi, 31 D. immitis, A. caninum, T. colubriformis, A. cantonensis, and Teladorsagia circumcincta. 8,[32][33][34] Galectin proteins show β-galactoside affinity, and they are structurally characterized by a carbohydrate recognition domain, which codes information for cell-to-cell and cell-to-extracellular matrix interactions; 35 they also mediate the invasion into host, and participate in maintaining infection and modulating the host immune response. 36 Although galectins of the parasitic helminthes have been poorly studied, two recombinant galectins of Haemonchus contortus (rHco-gal-m and rHco-gal-f) were used for vaccination of 9-10-month-old goats against infection by this parasite; the application of 100 μg of protein reduced fecal egg output and worm burdens by 37.25% and 41.1%, respectively.…”

Human and Animal Dirofilariasis: the Emergence of a Zoonotic Mosaic

“…Many data confirm the link between Wolbachia and inflammation when adult worms die. Most patients diagnosed with pulmonary dirofilariasis demonstrate an exclusively IgG1-based (Th1) proinflammatory response to WSP (390,396), whereas individuals exposed to D. immitis without pulmonary nodules exhibit a predominantly IgEbased (Th2) response (129,344) that is specifically stimulated by both a galectin and an aldolase from the parasite but not by Wolbachia (344). In agreement with these data, the immunization of BALB/c mice with recombinant WSP induced the expression of iNOS and gamma interferon (IFN-␥) mRNA and the production of NO and IgG2a (Th1), which are related to macrophage-mediated proinflammatory responses (55,287).…”