Abstract
Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg population by secreting products that activate TGF-β signalling, but the identity of the active molecule is unknown. Here we identify an H. polygyrus TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3+ Treg cells. Hp-TGM has no homology with mammalian TGF-β or other members of the TGF-β family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, Helminth / chemistry
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Antigens, Helminth / genetics
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Antigens, Helminth / immunology
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Female
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Helminth Proteins / chemistry
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Helminth Proteins / genetics
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Helminth Proteins / immunology
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Host-Pathogen Interactions / genetics
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Host-Pathogen Interactions / immunology
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Humans
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Immune Evasion / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Transgenic
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Molecular Mimicry / genetics
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Molecular Mimicry / immunology*
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Nematospiroides dubius / genetics
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Nematospiroides dubius / immunology*
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Nematospiroides dubius / pathogenicity*
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Protein Binding
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Protein Domains
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Receptors, Transforming Growth Factor beta / metabolism
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Strongylida Infections / immunology
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Strongylida Infections / parasitology
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T-Lymphocytes, Regulatory / immunology*
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Transforming Growth Factor beta / metabolism*
Substances
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Antigens, Helminth
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Helminth Proteins
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Receptors, Transforming Growth Factor beta
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Transforming Growth Factor beta