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Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Cadman, E T; Thysse, K A; Bearder, S; Cheung, A Y N; Johnston, A C; Lee, J J; Lawrence, R A

Authors

E T Cadman

K A Thysse

S Bearder

A Y N Cheung

A C Johnston

J J Lee

R A Lawrence



Abstract

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity.

Citation

Cadman, E. T., Thysse, K. A., Bearder, S., Cheung, A. Y. N., Johnston, A. C., Lee, J. J., & Lawrence, R. A. (2014). Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae. PLoS Pathogens, 10(3), e1003988. https://doi.org/10.1371/journal.ppat.1003988

Journal Article Type Article
Acceptance Date Jan 27, 2014
Publication Date Mar 13, 2014
Deposit Date Nov 12, 2014
Publicly Available Date Mar 28, 2024
Journal PLoS Pathogens
Print ISSN 1553-7366
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 10
Issue 3
Pages e1003988
DOI https://doi.org/10.1371/journal.ppat.1003988
Public URL https://rvc-repository.worktribe.com/output/1405849
Additional Information Corporate Creators : Mayo Clinic Arizona

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