Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma
Author(s)
Navarro, Severine
Pickering, Darren A
Ferreira, Ivana B
Jones, Linda
Ryan, Stephanie
Troy, Sally
Leech, Andrew
Hotez, Peter J
Zhan, Bin
Laha, Thewarach
Prentice, Roger
Sparwasser, Tim
Croese, John
Engwerda, Christian R
Upham, John W
et al.
Griffith University Author(s)
Year published
2016
Metadata
Show full item recordAbstract
In the developed world, declining prevalence of some parasitic infections correlateswith increased incidence of allergic and autoimmune disorders. Moreover, experimental human infection with some parasitic worms confers protection against inflammatory diseases in phase 2 clinical trials. Parasitic worms manipulate the immune system by secreting immunoregulatorymolecules that offer promise as a novel therapeutic modality for inflammatory diseases.We identify a protein secreted by hookworms, anti-inflammatory protein-2 (AIP-2), that suppressed airway inflammation in amouse model of asthma, reduced expression of costimulatory ...
View more >In the developed world, declining prevalence of some parasitic infections correlateswith increased incidence of allergic and autoimmune disorders. Moreover, experimental human infection with some parasitic worms confers protection against inflammatory diseases in phase 2 clinical trials. Parasitic worms manipulate the immune system by secreting immunoregulatorymolecules that offer promise as a novel therapeutic modality for inflammatory diseases.We identify a protein secreted by hookworms, anti-inflammatory protein-2 (AIP-2), that suppressed airway inflammation in amouse model of asthma, reduced expression of costimulatory markers on human dendritic cells (DCs), and suppressed proliferation ex vivo of T cells from human subjects with house dust mite allergy. In mice, AIP-2 was primarily captured by mesenteric CD103+ DCs and suppression of airway inflammation was dependent on both DCs and Foxp3+ regulatory T cells (Tregs) that originated in the mesenteric lymph nodes (MLNs) and accumulated in distant mucosal sites. Transplantation of MLNs from AIP-2-treatedmice into naïve hosts revealed a lymphoid tissue conditioning that promoted Treg induction and long-term maintenance. Our findings indicate that recombinant AIP-2 could serve as a novel curative therapeutic for allergic asthma and potentially other inflammatory diseases.
View less >
View more >In the developed world, declining prevalence of some parasitic infections correlateswith increased incidence of allergic and autoimmune disorders. Moreover, experimental human infection with some parasitic worms confers protection against inflammatory diseases in phase 2 clinical trials. Parasitic worms manipulate the immune system by secreting immunoregulatorymolecules that offer promise as a novel therapeutic modality for inflammatory diseases.We identify a protein secreted by hookworms, anti-inflammatory protein-2 (AIP-2), that suppressed airway inflammation in amouse model of asthma, reduced expression of costimulatory markers on human dendritic cells (DCs), and suppressed proliferation ex vivo of T cells from human subjects with house dust mite allergy. In mice, AIP-2 was primarily captured by mesenteric CD103+ DCs and suppression of airway inflammation was dependent on both DCs and Foxp3+ regulatory T cells (Tregs) that originated in the mesenteric lymph nodes (MLNs) and accumulated in distant mucosal sites. Transplantation of MLNs from AIP-2-treatedmice into naïve hosts revealed a lymphoid tissue conditioning that promoted Treg induction and long-term maintenance. Our findings indicate that recombinant AIP-2 could serve as a novel curative therapeutic for allergic asthma and potentially other inflammatory diseases.
View less >
Journal Title
Science Translational Medicine
Volume
8
Issue
362
Subject
Biological sciences
Biomedical and clinical sciences
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine