DOI: 10.4049/jimmunol.164.12.6453. A Filarial Nematode-Secreted Product Signals Dendritic Cells to Acquire a Phenotype That Drives Development of Th2 Cells

A Filarial Nematode-Secreted Product Signals Dendritic Cells to Acquire a Phenotype That Drives Development of Th2 Cells

10.4049/jimmunol.164.12.6453

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract Although exogeneous “danger” signals such as LPS can activate APC to produce a Th1 response, the nature of events initiating a Th2 response is controversial. We now show that pathogen-derived products have the capacity to induce bone marrow-derived dendritic cell cultures to acquire a phenotype that promotes the differentiation of naive CD4+ T cells toward either a Th1 or Th2 phenotype. Thus, LPS-matured dendritic cells (DC1) promote a Th1 response (increased generation of IFN-γ and reduced production of IL-4) by Ag-stimulated CD4+ T cells from the DO.11.10 transgenic mouse expressing a TCR specific for an OVA peptide (OVA323–339). In contrast, a phosphorylcholine-containing glycoprotein, ES-62, secreted by the filarial nematode, Acanthocheilonema viteae, which generates a Th2 Ab response in vivo, is found to induce the maturation of dendritic cells (DC2) with the capacity to induce Th2 responses (increased IL-4 and decreased IFN-γ). In addition, we show that the switch to either Th1 or Th2 responses is not effected by differential regulation through CD80 or CD86 and that a Th2 response is achieved in the presence of IL-12.

Bibliography

Whelan, M., Harnett, M. M., Houston, K. M., Patel, V., Harnett, W., & Rigley, K. P. (2000). A Filarial Nematode-Secreted Product Signals Dendritic Cells to Acquire a Phenotype That Drives Development of Th2 Cells. The Journal of Immunology, 164(12), 6453â6460.

Authors 6

Michael Whelan (first)
Margaret M. Harnett (additional)
Katrina M. Houston (additional)
Vanshree Patel (additional)
William Harnett (additional)
Kevin P. Rigley (additional)

References 30 Referenced 273

Dates

Type	When
Created	11 years, 4 months ago (April 20, 2014, 9:59 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 2, 2025, 11:57 a.m.)
Indexed	4 months, 3 weeks ago (March 31, 2025, 3:23 a.m.)
Issued	25 years, 2 months ago (June 15, 2000)
Published	25 years, 2 months ago (June 15, 2000)
Published Print	25 years, 2 months ago (June 15, 2000)

Funders 0

None

BibTeX

@article{Whelan_2000, title={A Filarial Nematode-Secreted Product Signals Dendritic Cells to Acquire a Phenotype That Drives Development of Th2 Cells}, volume={164}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.164.12.6453}, DOI={10.4049/jimmunol.164.12.6453}, number={12}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Whelan, Michael and Harnett, Margaret M. and Houston, Katrina M. and Patel, Vanshree and Harnett, William and Rigley, Kevin P.}, year={2000}, month=jun, pages={6453–6460} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        3,
        31
      ]
    ],
    "date-time": "2025-03-31T07:23:42Z",
    "timestamp": 1743405822273,
    "version": "3.32.0"
  },
  "reference-count": 30,
  "publisher": "Oxford University Press (OUP)",
  "issue": "12",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2000,
        6,
        15
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>Although exogeneous \u201cdanger\u201d signals such as LPS can activate APC to produce a Th1 response, the nature of events initiating a Th2 response is controversial. We now show that pathogen-derived products have the capacity to induce bone marrow-derived dendritic cell cultures to acquire a phenotype that promotes the differentiation of naive CD4+ T cells toward either a Th1 or Th2 phenotype. Thus, LPS-matured dendritic cells (DC1) promote a Th1 response (increased generation of IFN-\u03b3 and reduced production of IL-4) by Ag-stimulated CD4+ T cells from the DO.11.10 transgenic mouse expressing a TCR specific for an OVA peptide (OVA323\u2013339). In contrast, a phosphorylcholine-containing glycoprotein, ES-62, secreted by the filarial nematode, Acanthocheilonema viteae, which generates a Th2 Ab response in vivo, is found to induce the maturation of dendritic cells (DC2) with the capacity to induce Th2 responses (increased IL-4 and decreased IFN-\u03b3). In addition, we show that the switch to either Th1 or Th2 responses is not effected by differential regulation through CD80 or CD86 and that a Th2 response is achieved in the presence of IL-12.</jats:p>",
  "DOI": "10.4049/jimmunol.164.12.6453",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2014,
        4,
        21
      ]
    ],
    "date-time": "2014-04-21T01:59:29Z",
    "timestamp": 1398045569000
  },
  "page": "6453-6460",
  "source": "Crossref",
  "is-referenced-by-count": 273,
  "title": "A Filarial Nematode-Secreted Product Signals Dendritic Cells to Acquire a Phenotype That Drives Development of Th2 Cells",
  "prefix": "10.1093",
  "volume": "164",
  "author": [
    {
      "given": "Michael",
      "family": "Whelan",
      "sequence": "first",
      "affiliation": [
        {
          "name": "*The Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom;"
        }
      ]
    },
    {
      "given": "Margaret M.",
      "family": "Harnett",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "\u2020Department of Immunology, University of Glasgow, Glasgow, United Kingdom; and"
        }
      ]
    },
    {
      "given": "Katrina M.",
      "family": "Houston",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "\u2021Department of Immunology, University of Strathclyde, Glasgow, United Kingdom"
        }
      ]
    },
    {
      "given": "Vanshree",
      "family": "Patel",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "*The Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom;"
        }
      ]
    },
    {
      "given": "William",
      "family": "Harnett",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "\u2021Department of Immunology, University of Strathclyde, Glasgow, United Kingdom"
        }
      ]
    },
    {
      "given": "Kevin P.",
      "family": "Rigley",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "*The Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom;"
        }
      ]
    }
  ],
  "member": "286",
  "reference": [
    {
      "key": "2022123115191264700_R1",
      "doi-asserted-by": "crossref",
      "unstructured": "Mosmann, T. R.,  J. H. Schumacher,  N. F. Street,  R. Budd,  A. T. A. O\u2019Garra,  M. W. Fong,  K. W. Bond,  A. Sher Moore,  D. F. Fiorentino.  1991. Diversity of cytokine synthesis and function of mouse CD4+ T cells. Immunol. Rev.\u2008123: 209",
      "DOI": "10.1111/j.1600-065X.1991.tb00612.x"
    },
    {
      "key": "2022123115191264700_R2",
      "doi-asserted-by": "crossref",
      "unstructured": "Mosmann, T. R.,  S. Sad.  1996. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol. Today\u200817: 138",
      "DOI": "10.1016/0167-5699(96)80606-2"
    },
    {
      "key": "2022123115191264700_R3",
      "doi-asserted-by": "crossref",
      "unstructured": "Hilkens, C. M.,  P. Kalinski,  M. de Boer,  M. L. Kapsenberg.  1997. Human dendritic cells require exogenous interleukin-12-inducing factors to direct the development of naive T-helper cells toward the Th1 phenotype. Blood\u200890: 1920",
      "DOI": "10.1182/blood.V90.5.1920"
    },
    {
      "key": "2022123115191264700_R4",
      "doi-asserted-by": "crossref",
      "unstructured": "Banchereau, J.,  R. M. Steinman.  1998. Dendritic cells and the control of immunity. Nature\u2008392: 245",
      "DOI": "10.1038/32588"
    },
    {
      "key": "2022123115191264700_R5",
      "doi-asserted-by": "crossref",
      "unstructured": "Flynn, S.,  K. M. Toellner,  C. Raykundalia,  M. Goodall,  P. Lane.  1998. CD4 T cell cytokine differentiation: the B cell activation molecule, OX40 ligand, instructs CD4 T cells to express interleukin 4 and upregulates expression of the chemokine receptor, Blr-1. J. Exp. Med.\u2008188: 297",
      "DOI": "10.1084/jem.188.2.297"
    },
    {
      "key": "2022123115191264700_R6",
      "doi-asserted-by": "crossref",
      "unstructured": "Rissoan, M.-C.,  V. Soumelis,  N. Kadowaki,  G. Grouard,  F. Briere,  R. Malefyt,  Y.-J. Liu.  1999. Reciprical control of T helper cell and dendritic cell differentiation. Science\u2008283: 1183",
      "DOI": "10.1126/science.283.5405.1183"
    },
    {
      "key": "2022123115191264700_R7",
      "doi-asserted-by": "crossref",
      "unstructured": "Toellner, K. M.,  S. A. Luther,  D. M. Sze,  R. K. Choy,  D. R. Taylor,  I. C. M. MacLennan,  H. Acha Orbea.  1998. T helper 1 (Th1) and Th2 characteristics start to develop during T cell priming and are associated with an immediate ability to induce immunoglobulin class switching. J. Exp. Med.\u2008187: 1193",
      "DOI": "10.1084/jem.187.8.1193"
    },
    {
      "key": "2022123115191264700_R8",
      "doi-asserted-by": "crossref",
      "unstructured": "Hsieh, C. S.,  S. E. Macatonia,  C. S. Tripp,  S. F. Wolf,  A. O\u2019Garra,  K. M. Murphy.  1993. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science\u2008260: 547",
      "DOI": "10.1126/science.8097338"
    },
    {
      "key": "2022123115191264700_R9",
      "doi-asserted-by": "crossref",
      "unstructured": "Hosken, N. A.,  K. Shibuya,  A. W. Heath,  K. M. Murphy,  A. O\u2019Garra.  1995. The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor-\u03b1\u03b2-transgenic model. J. Exp. Med.\u2008182: 1579",
      "DOI": "10.1084/jem.182.5.1579"
    },
    {
      "key": "2022123115191264700_R10",
      "doi-asserted-by": "crossref",
      "unstructured": "Yazdanbakhsh, M.,  W. A. Paxton,  Y. C. Kruize,  E. Sartono,  A. Kurniawan,  A. van het Wout,  M. E. Selkirk,  F. Partono,  R. M. Maizels.  1993. T cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis. J. Infect. Dis.\u2008167: 925",
      "DOI": "10.1093/infdis/167.4.925"
    },
    {
      "key": "2022123115191264700_R11",
      "doi-asserted-by": "crossref",
      "unstructured": "Harnett, W.,  M. M. Harnett.  1999. Phosphorylcholine: friend or foe of the immune system?. Immunol. Today\u200820: 125",
      "DOI": "10.1016/S0167-5699(98)01419-4"
    },
    {
      "key": "2022123115191264700_R12",
      "doi-asserted-by": "crossref",
      "unstructured": "Harnett, W.,  K. M. Houston,  R. Amess,  M. J. Worms.  1993. Acanthocheilonema viteae: phosphorylcholine is attached to the major excretory-secretory product via an N-linked glycan. Exp. Parasitol.\u200877: 498",
      "DOI": "10.1006/expr.1993.1113"
    },
    {
      "key": "2022123115191264700_R13",
      "doi-asserted-by": "crossref",
      "unstructured": "Inaba, K.,  M. Inaba,  N. Romani,  H. Aya,  M. Deguchi,  S. Ikehara,  S. Muramatsu,  R. M. Steinman.  1992. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J. Exp. Med.\u2008176: 1693",
      "DOI": "10.1084/jem.176.6.1693"
    },
    {
      "key": "2022123115191264700_R14",
      "doi-asserted-by": "crossref",
      "unstructured": "Constant, S.,  C. Pfeiffer,  A. Woodard,  T. Pasqualini,  K. Bottomly.  1995. Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells. J. Exp. Med.\u2008182: 1591",
      "DOI": "10.1084/jem.182.5.1591"
    },
    {
      "key": "2022123115191264700_R15",
      "doi-asserted-by": "crossref",
      "unstructured": "Kalinski, P.,  C. M. Hilkens,  A. Snijders,  F. G. Snijdewint,  M. L. Kapsenberg.  1997. Dendritic cells, obtained from peripheral blood precursors in the presence of PGE2, promote Th2 responses. Adv. Exp. Med. Biol.\u2008417: 363",
      "DOI": "10.1007/978-1-4757-9966-8_59"
    },
    {
      "key": "2022123115191264700_R16",
      "doi-asserted-by": "crossref",
      "unstructured": "Buelens, C.,  V. Verhasselt,  D. De Groote,  K. Thielemans,  M. Goldman,  F. Willems.  1997. Human dendritic cell responses to lipopolysaccharide and CD40 ligation are differentially regulated by interleukin-10. Eur. J. Immunol.\u200827: 1848",
      "DOI": "10.1002/eji.1830270805"
    },
    {
      "key": "2022123115191264700_R17",
      "doi-asserted-by": "crossref",
      "unstructured": "Cleveland, M. G.,  J. D. Gorham,  T. L. Murphy,  E. Tuomanen,  K. M. Murphy.  1996. Lipoteichoic acid preparations of gram-positive bacteria induce interleukin-12 through a CD14-dependent pathway. Infect. Immun.\u200864: 1906",
      "DOI": "10.1128/iai.64.6.1906-1912.1996"
    },
    {
      "key": "2022123115191264700_R18",
      "doi-asserted-by": "crossref",
      "unstructured": "O\u2019Garra, A. S. E.,  C. S. Hsieh Macatonia,  K. M. Murphy.  1993. Regulatory role of IL-4 and other cytokines in T helper cell development in an \u03b1\u03b2 TCR transgenic mouse system. Res. Immunol.\u2008144: 620",
      "DOI": "10.1016/S0923-2494(05)80014-8"
    },
    {
      "key": "2022123115191264700_R19",
      "doi-asserted-by": "crossref",
      "unstructured": "O\u2019Garra, A..  1999. Checkpoints for regulation of development and IFN-\u03b3 production by Th1 cells in TCR-transgenic models. Immunol. Lett.\u200865: 41",
      "DOI": "10.1016/S0165-2478(98)00122-9"
    },
    {
      "key": "2022123115191264700_R20",
      "doi-asserted-by": "crossref",
      "unstructured": "Schmitt, E.,  P. Hoehn,  T. Germann,  E. Rude.  1994. Differential effects of interleukin-12 on the development of naive mouse CD4+ T cells. Eur. J. Immunol.\u200824: 343",
      "DOI": "10.1002/eji.1830240211"
    },
    {
      "key": "2022123115191264700_R21",
      "doi-asserted-by": "crossref",
      "unstructured": "Hosken, N. A.,  K. Shibuya,  A. W. Heath,  K. M. Murphy,  A. O\u2019Garra.  1995. The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor-\u03b1\u03b2-transgenic model. J. Exp. Med.\u2008182: 1579",
      "DOI": "10.1084/jem.182.5.1579"
    },
    {
      "key": "2022123115191264700_R22",
      "doi-asserted-by": "crossref",
      "unstructured": "Medzhitov, R.,  C. A. Janeway, Jr.  1997. Innate immunity: the virtues of a nonclonal system of recognition. Cell\u200891: 295",
      "DOI": "10.1016/S0092-8674(00)80412-2"
    },
    {
      "key": "2022123115191264700_R23",
      "doi-asserted-by": "crossref",
      "unstructured": "Lenschow, D. J.,  K. C. Herold,  L. Rhee,  B. Patel,  A. Koons,  H. Y. Qin,  E. Fuchs,  B. Singh,  C. B. Thompson,  J. A. Bluestone.  1996. CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes. [Published erratum appears in 1997 Immunity 6:215.]. Immunity\u20085: 285",
      "DOI": "10.1016/S1074-7613(00)80323-4"
    },
    {
      "key": "2022123115191264700_R24",
      "doi-asserted-by": "crossref",
      "unstructured": "Schweitzer, A. N.,  F. Borriello,  R. C. Wong,  A. K. Abbas,  A. H. Sharpe.  1997. Role of costimulators in T cell differentiation: studies using antigen-presenting cells lacking expression of CD80 or CD86. J. Immunol.\u2008158: 2713",
      "DOI": "10.4049/jimmunol.158.6.2713"
    },
    {
      "key": "2022123115191264700_R25",
      "doi-asserted-by": "crossref",
      "unstructured": "Rulifson, I. C.,  A. I. Sperling,  P. E. Fields,  F. W. Fitch,  J. A. Bluestone.  1997. CD28 Co-stimulation promotes the production of TH2 cytokines. J. Immunol.\u2008158: 658",
      "DOI": "10.4049/jimmunol.158.2.658"
    },
    {
      "key": "2022123115191264700_R26",
      "doi-asserted-by": "crossref",
      "unstructured": "Salomon, B.,  J. A. Bluestone.  1998. LFA-1 interaction with ICAM-1 and ICAM-2 regulates Th2 cytokine production. J. Immunol.\u2008161: 5138",
      "DOI": "10.4049/jimmunol.161.10.5138"
    },
    {
      "key": "2022123115191264700_R27",
      "doi-asserted-by": "crossref",
      "unstructured": "Ravichandran, M.,  S. Mahanty,  V. Kumaraswami,  T. B. Nutman,  K. Jayaraman.  1997. Elevated IL-10 mRNA expression and downregulation of Th1-type cytokines in microfilaraemic individuals with Wuchereria bancrofti infection. Parasite Immunol.\u200819: 69",
      "DOI": "10.1046/j.1365-3024.1997.d01-185.x"
    },
    {
      "key": "2022123115191264700_R28",
      "doi-asserted-by": "crossref",
      "unstructured": "Palanivel, V.,  C. Posey,  A. M. Horauf,  W. Solbach,  W. F. Piessens,  D. A. Harn.  1996. B-cell outgrowth and ligand-specific production of IL-10 correlate with Th2 dominance in certain parasitic diseases. Exp. Parasitol.\u200884: 168",
      "DOI": "10.1006/expr.1996.0102"
    },
    {
      "key": "2022123115191264700_R29",
      "doi-asserted-by": "crossref",
      "unstructured": "Urban, B. C.,  D. J. Ferguson,  A. Pain,  N. Willcox,  M. Plebanski,  J. M. Austyn,  D. J. Roberts.  1999. Plasmodium\u2008falciparum-infected erythrocytes modulate the maturation of dendritic cells. Nature\u2008400: 73",
      "DOI": "10.1038/21900"
    },
    {
      "key": "2022123115191264700_R30",
      "doi-asserted-by": "crossref",
      "unstructured": "Van Overtvelt, L.,  N. Vanderheyde,  V. Verhasselt,  J. Ismaili,  L. De Vos,  M. Goldman,  F. Willems,  B. Vray.  1999. Trypanosoma cruzi infects human dendritic cells and prevents their maturation: inhibition of cytokines, HLA-DR, and costimulatory molecules. Infect. Immun.\u200867: 4033",
      "DOI": "10.1128/IAI.67.8.4033-4040.1999"
    }
  ],
  "container-title": "The Journal of Immunology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.aai.org/jimmunol/article-pdf/164/12/6453/1114818/6453.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://journals.aai.org/jimmunol/article-pdf/164/12/6453/1114818/6453.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2025,
        1,
        2
      ]
    ],
    "date-time": "2025-01-02T16:57:19Z",
    "timestamp": 1735837039000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.aai.org/jimmunol/article/164/12/6453/33113/A-Filarial-Nematode-Secreted-Product-Signals"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2000,
        6,
        15
      ]
    ]
  },
  "references-count": 30,
  "journal-issue": {
    "issue": "12",
    "published-print": {
      "date-parts": [
        [
          2000,
          6,
          15
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.4049/jimmunol.164.12.6453",
  "relation": {},
  "ISSN": [
    "0022-1767",
    "1550-6606"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2000,
        6,
        15
      ]
    ]
  }
}