Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae
| Autor: | Ashleigh C. Johnston, Emma T. Cadman, James J. Lee, Katherine A. Thysse, Anita Y. N. Cheung, Rachel A. Lawrence, Siobhan Bearder |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Pathology medicine.medical_treatment Immunoglobulin E Mice 0302 clinical medicine lcsh:QH301-705.5 Microfilariae Mice Knockout 0303 health sciences biology respiratory system Mast cell Acquired immune system Innate Immunity 3. Good health Filariasis medicine.anatomical_structure Cytokine Eosinophil peroxidase Research Article lcsh:Immunologic diseases. Allergy medicine.medical_specialty Immunology Enzyme-Linked Immunosorbent Assay Immunopathology Microbiology 03 medical and health sciences Immune system Virology Genetics medicine Animals Molecular Biology Biology Immunity to Infections Brugia malayi 030304 developmental biology Goblet cell Immunity Immune Defense Eosinophil Eosinophils Mice Inbred C57BL Disease Models Animal lcsh:Biology (General) biology.protein Parasitology lcsh:RC581-607 030215 immunology |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 10, Iss 3, p e1003988 (2014) |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | 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. Author Summary Eosinophil recruitment is a classic characteristic of both allergic and parasitic helminth diseases. Elucidation of the role of eosinophils in these diseases is of pivotal importance for understanding the mechanisms of protection and the development of pathology. In the last few years, the part played by eosinophils in helminth-defence has been dissected using in vivo models and their importance in protection has been shown to be highly specific to the host-parasite combination. This study dissects the role of eosinophils during infection with the human lymphatic filarial parasite, Brugia malayi, which causes the major neglected tropical disease, lymphatic filariasis. In particular, we study the role of the eosinophil as a double–edged sword in generating both protection and pathology. We definitively confirm the importance of eosinophils in protection against B. malayi microfilariae and show that protection is not mediated by release of the eosinophil granule proteins, major basic protein or eosinophil peroxidase alone. Overall, we reveal that during an infection with B. malayi microfilariae, eosinophils are critical for primary protective responses. However, eosinophils contribute to nematode-induced lung dysfunction, while additionally, eosinophil granules are important negative regulators of parasite-induced lung inflammatory and some adaptive immune responses. |
| Databáze: | OpenAIRE |
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