title: Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma.
abstract: In the developed world, declining prevalence of some parasitic infections correlates with 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 immunoregulatory molecules 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 a mouse 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-treated mice into naïve hosts revealed a lymphoid tissue conditioning that promoted Treginduction 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.
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia. severine.navarro@jcu.edu.au alex.loukas@jcu.edu.au.
authors: Severine
authors: S
authors: Navarro
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors: Darren A
authors: DA
authors: Pickering
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors: Ivana B
authors: IB
authors: Ferreira
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors: Linda
authors: L
authors: Jones
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors: Stephanie
authors: S
authors: Ryan
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors: Sally
authors: S
authors: Troy
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors: Andrew
authors: A
authors: Leech
authors: Baylor College of Medicine, Houston, TX 77030, USA.
authors: Peter J
authors: PJ
authors: Hotez
authors: Baylor College of Medicine, Houston, TX 77030, USA.
authors: Bin
authors: B
authors: Zhan
authors: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Thewarach
authors: T
authors: Laha
authors: Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors: Roger
authors: R
authors: Prentice
authors: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
authors: Tim
authors: T
authors: Sparwasser
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.|Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors: John
authors: J
authors: Croese
authors: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors: Christian R
authors: CR
authors: Engwerda
authors: University of Queensland, Brisbane, Queensland, Australia.|Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors: John W
authors: JW
authors: Upham
authors: CNRS UMR7275, INSERM U1080, Université de Nice Sophia Antipolis, Nice, France.
authors: Valerie
authors: V
authors: Julia
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors: Paul R
authors: PR
authors: Giacomin
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia. severine.navarro@jcu.edu.au alex.loukas@jcu.edu.au.
authors: Alex
authors: A
authors: Loukas
mesh_terms: D000328:Adult; D000723:Ancylostomatoidea; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001249:Asthma / Q000097:blood* / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015801:Helminth Proteins / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation; D039001:Integrin alpha Chains / Q000378:metabolism; D008297:Male; D051379:Mice; D009092:Mucous Membrane / Q000378:metabolism; D015995:Prevalence; D039981:Pyroglyphidae; D011994:Recombinant Proteins / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D015801:Helminth Proteins; D039001:Integrin alpha Chains; D011994:Recombinant Proteins; C091367:alpha E integrins; D007073:Immunoglobulin E