Identification and characterization of a novel nematode pan allergen (NPA) from Wuchereria bancrofti and their potential role in human filarial tropical pulmonary eosinophilia (TPE)

Abstract

Background

Tropical pulmonary eosinophilia (TPE) is a chronic respiratory syndrome associated with Lymphatic Filariasis (LF), a tropical parasitic infection of the human, transmitted by mosquitoes. The larval form of LF (microfilariae) are trapped in the lungs of TPE subjects have a major role in initiating the TPE syndrome. To date, there are no reports on the potential allergen that is responsible for generating parasite-specific IgE in TPE.

Methodology/Principal findings

In this project, we screened a cDNA expression library of the microfilarial stages of Wuchereria bancrofti with monoclonal IgE antibodies prepared from subjects with clinical filarial infections. Our studies identified a novel molecule that showed significant sequence similarity to an allergen. A blast analysis showed the presence of similar proteins in a number of nematodes parasites. Thus, we named this molecule as Nematode Pan Allergen (NPA). Subsequent functional analysis showed that NPA is a potent allergen that can cause release of histamine from mast cells, induce secretion of proinflammatory cytokines from alveolar macrophages and promote accumulation of eosinophils in the tissue, all of which occur in TPE lungs.

Conclusions/Significance

Based on our results, we conclude that the NPA protein secreted by the microfilariae of W. bancrofti may play a significant role in the pathology of TPE syndrome in LF infected individuals. Further studies on this molecule can help design an approach to neutralize the NPA in an attempt to reduce the pathology associated with TPE in LF infected subjects.

Author summary

Lymphatic filariasis, commonly called as elephantiasis is a gruesome disfiguring disease caused by parasitic worms. Some of the infected individuals develop asthma like hypersensitivity reaction called Tropical Pulmonary Eosinophilia (TPE), which can be fatal. TPE is believed to be caused by allergens released by the larval (microfilariae) stages of the lymphatic filarial worms in the lung blood vessels. However, no potential allergen have been described to date that is responsible for causing the TPE symptoms. In this study we screened a phage display cDNA expression library of the microfilariae stages of the lymphatic filarial parasite with IgE monoclonal antibodies prepared from subjects with lymphatic filarial infections, some of these individuals also exhibited TPE clinical symptoms. This approach identified a novel nematode specific pan allergen (NPA). When tested in the laboratory, NPA showed that it can trigger histamine release from mast cells, trigger inflammatory responses in lung cells and can cause accumulation of eosinophils in the tissue. All these are typical clinical symptoms of TPE. Thus, we conclude in this study that targeting the NPA can be a potential treatment option for alleviating the allergy and hypersensitivity reactions such as in TPE during parasitic infections.