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

• Published in: PLoS neglected tropical diseases Vol. 18; no. 2; p. e0011972
• Main Authors: Katru, Samuel Christopher, Balakrishnan, Anand Setty, Munirathinam, Gnanasekar, Hadadianpour, Azadeh, Smith, Scott A., Kalyanasundaram, Ramaswamy
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2024; Public Library of Science (PLoS)
• Subjects: Allergens; Allergies; Alveoli; Antibodies; Aquatic insects; Biology and life sciences; Chronic infection; Cloning; Complementary DNA; Cytokines; Eosinophilia; Eosinophils; Females; Filariasis; Functional analysis; Histamine; Immunoglobulin E; Infections; Inflammation; Leukocytes (eosinophilic); Lung diseases; Lungs; Macrophages; Mast cells; Medicine and Health Sciences; Monoclonal antibodies; Mosquitoes; Nematodes; Parasites; Parasitic diseases; Pathology; Proteins; Research and Analysis Methods; Respiratory diseases; Tropical diseases; Vector-borne diseases; Wuchereria bancrofti; United States > US; Illinois
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0011972

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. 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. 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.