Induction of histamine release in parasitized individuals by somatic and cuticular antigens from Onchocerca volvulus.

Abstract

Abstract. The host immune response in onchocerciasis is believed to contribute to the clinical manifestations of infection. Mazzotti and chronic inflammatory reactions might be mediated by mechanisms involving specific IgE and reactivity of mast cells and basophils to the parasite antigens. In this report, we show that Onchocerca volvulus antigens are capable of inducing histamine release. Three types of extracts were prepared from the parasite: soluble total, surface, and cuticular collagen. Soluble extracts released histamine in all individuals with onchocerciasis at significantly higher levels (P Ͻ 0.05) than those found in endemic controls, but similar levels to those found in patients with mansonellosis. However, cuticular collagen induced significantly (P Ͻ 0.01) higher histamine release in patients with onchocerciasis than in those with mansonellosis. No reactivity against human type IV collagen was observed. Implications derived from the presence of sensitized basophils in the pathogenesis of onchocerciasis are discussed.Onchocerciasis is an endemic disease in several areas of Africa and Latin America. The main clinical manifestations are related to the presence of microfilariae inducing a chronic inflammatory response in tissues, particularly in the skin and eyes. It is believed that the host immune response contributes to the pathologic consequences of infection. The cellular immune response in patients with generalized microfiladermia is characterized by minimal proliferation to onchocercal antigens; however, healthy individuals from some endemic areas show higher proliferation rates.1-3 Nonspecific suppression of streptococcal antigen-induced lymphocyte reactivity has also been reported both in patients and healthy individuals from endemic areas. 2 This suppression is agerelated, being higher in older patients. The underlying mechanism of this down-regulation of cell-mediated immunity is not clearly understood, but in some patients, exogenous interleukin-2 restored reactivity to parasite antigen.3 The humoral immune response is characterized by the presence of specific antibodies to multiple parasite antigens. 4 Many people with onchocerciasis show high levels of serum IgE. 5 Even though most of the IgE detected in helminthiasis is nonspecific IgE,6 it is possible that IgE antibody could be involved in acute inflammatory complications of Onchocerca volvulus infection. Some infected individuals show severe local dermatitis with few microfilariae (sowda) and significantly higher IgE titers than patients with generalized onchocerciasis. 7 In lymphatic filariasis, it has been demonstrated that despite the presence of basophils and mast cells sensitized with antiparasite IgE, the allergic reactivity is controlled by blocking antibodies. 8 An interesting model of onchocercal pathogenesis is provided by animal onchocercal ocular disease, in which intracorneal injection of microfilariae in sensitized animals induces local pathology and specific IgE production.9 These reports support the hypothesis that IgE-m...

Lack of Basophilia in Human Parasitic Infections

“…22 Basophils from Toxocara-, Ascaris-, Onchocerca-, Wuchereria-, Strongyloides-, and Schistosoma-infected patients have been shown to release histamine in response to parasite antigen. [23][24][25][26][27] The amount of histamine released by basophils in response to Toxocara antigen was found to be proportional to the serum concentration of Toxocara antigen-specific IgE. 23 In addition to high levels of IgE, human helminth infections are also associated with increased production of interleukin (IL)-4, the prototypical Th2 cytokine.…”

Granulocytes: effector cells or immunomodulators in the immune response to helminth infection?

“…Despite this paucity of reports of raised basophils in human helminth infections, basophils from humans infected with Toxocara canis, O. volvulus, W. bancrofti, Loa loa, S. stercoralis and Schistosoma sp. all release histamine in response to parasite antigens in vitro (171,174–177). Basophils from filarial‐infected patients have been shown to release more IL‐4 per cell than CD4 + cells and at 100‐fold lower antigen concentration (178).…”

Parasite Antigen-Driven Basophils Are a Major Source of IL-4 in Human Filarial Infections

“…Basophils bind IgE through high affinity receptors (Fc⑀RI) on their surface and degranulate and release histamine and other inflammatory mediators after cross-linking of these receptors (4). Basophils from patients infected with Toxocara, Ascaris, Onchocerca, Wuchereria, Strongyloides, and Schistosoma have been shown to release histamine in response to parasite Ag (5)(6)(7)(8)(9), with the amount of histamine released proportional to the serum concentration of Ag-specific IgE (5).…”