Cell apoptosis induced by hookworm antigens: a strategy of immunomodulation.

Abstract

While several mechanisms of immunoregulation have been demonstrated for hookworm and other neglected tropical infections, the influence of apoptosis in the immunomodulation of hookworm infection is still poorly understood. In this study, we demonstrate the cytotoxic and pro-apoptotic activity of hookworm antigens in Jurkat T cells, mesenteric lymph nodes lymphocytes of healthy and hookworm-infected hamsters and during human natural infection. Our results showed that in vitrostimulation of Jurkat T cells with antigens induces a significant decrease of cell viability leading to a relevant increase of apoptotic cells. Similar results were also observed in experimental conditions, for both healthy and hookworm-infected hamsters` lymphocytes. Flow cytometric analysis demonstrated that hookworm-infected patients presented a significant increase of CD4+, CD8+, and CD19+lymphocytes in early and/or late apoptosis when compared with non-infected individuals. The downmodulation of TNF receptors, as well as the up-regulation of the pro-apoptotic genes belonging to the BCL-2 and P53 families, suggest that hookworm antigens induced apoptosis by an intrinsic mitochondrial pathway, acting as a sophisticated strategy to safeguard parasite long-term survival in their hosts.

• Authors: Pedro Henrique Gazzinelli-Guimarães, Elaine Maria Souza-Fagundes, Guilherme Grossi Lopes Cancado, Virgillio Gandra Martins, Lucas Carvalho Dhom-Lemos, Natasha Delaqua Ricci, Jacqueline Araujo Fiuza, Lilian Lacerda Bueno, Rodrigo Rodrigues Cambraia Miranda, Silvia Guatimosim, Andrea Gazzinelli, Rodrigo Correa-Oliveira, Daniella Castanheira Bartholomeu, Ricardo Toshio Fujiwara
• Journal: Frontiers in bioscience (Elite edition) (Front Biosci (Elite Ed)) Vol. 5 Issue 2 Pg. 662-75 (01 01 2013) ISSN: 1945-0508 [Electronic] Singapore
• PMID: 23277021 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Antigens, Helminth
• Propidium

Topics

• Animals
• Annexin A5
• Antigens, Helminth (immunology)
• Apoptosis (immunology)
• Brazil
• Cell Proliferation
• Cricetinae
• Flow Cytometry
• Hookworm Infections (immunology)
• Humans
• Immunomodulation (immunology)
• Jurkat Cells
• Lymph Nodes (chemistry)
• Mesentery (cytology)
• Microscopy, Confocal
• Propidium