{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:14:48Z","timestamp":1790248488509,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T00:00:00Z","timestamp":1291161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic helminth infections induce a type 2 immune response characterized by eosinophilia, high levels of IgE, and increased T cell production of type 2 cytokines. Because basophils have been shown to be substantial contributors of IL-4 in helminth infections, and because basophils are capable of inducing Th2 differentiation of CD4+ T cells and IgE isotype switching in B cells, we hypothesized that basophils function to amplify type 2 immune responses in chronic helminth infection. To test this, we evaluated basophil function using the Litomosoides sigmodontis filaria model of chronic helminth infection in BALB\/c mice. Time-course studies showed that eosinophilia, parasite Ag-specific CD4+ T cell production of IL-4 and IL-5 and basophil activation and IL-4 production in response to parasite Ag all peak late (6\u20138 wk) in the course of L. sigmodontis infection, after parasite-specific IgE has become detectable. Mixed-gender and single-sex worm implantation experiments demonstrated that the relatively late peak of these responses was not dependent on the appearance of circulating microfilariae, but may be due to initial low levels of parasite Ag load and\/or habitation of the developing worms in the pleural space. Depletion of basophils throughout the course of L. sigmodontis infection caused significant decreases in total and parasite-specific IgE, eosinophilia, and parasite Ag-driven CD4+ T cell proliferation and IL-4 production, but did not alter total worm numbers. These results demonstrate that basophils amplify type 2 immune responses, but do not serve a protective role, in chronic infection of mice with the filarial nematode L. sigmodontis.<\/jats:p>","DOI":"10.4049\/jimmunol.0903864","type":"journal-article","created":{"date-parts":[[2010,11,5]],"date-time":"2010-11-05T22:01:44Z","timestamp":1288994504000},"page":"7426-7434","source":"Crossref","is-referenced-by-count":48,"title":["Basophils Amplify Type 2 Immune Responses, but Do Not Serve a Protective Role, during Chronic Infection of Mice with the Filarial Nematode\n                    <i>Litomosoides sigmodontis<\/i>"],"prefix":"10.1093","volume":"185","author":[{"given":"Marina N","family":"Torrero","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc P","family":"H\u00fcbner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Karasuyama","sequence":"additional","affiliation":[{"name":"Department of Immune Regulation, Tokyo Medical and Dental University Graduate School , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Mitre","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,12,15]]},"reference":[{"key":"2025032412152295600_r1","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1128\/IAI.68.5.3034-3035.2000","article-title":"Role of gamma interferon and interleukin-4 in host defense against the human filarial parasite Brugia malayi","volume":"68","author":"Babu","year":"2000","journal-title":"Infect. Immun."},{"key":"2025032412152295600_r2","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.4049\/jimmunol.172.2.1139","article-title":"IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis","volume":"172","author":"Gurish","year":"2004","journal-title":"J. Immunol."},{"key":"2025032412152295600_r3","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.ijpara.2006.05.005","article-title":"Expression of IL-4 receptor on non-bone marrow-derived cells is necessary for the timely elimination of Strongyloides venezuelensis in mice, but not for intestinal IL-4 production","volume":"36","author":"Negr\u00e3o-Corr\u00eaa","year":"2006","journal-title":"Int. J. Parasitol."},{"key":"2025032412152295600_r4","doi-asserted-by":"crossref","first-page":"6078","DOI":"10.4049\/jimmunol.167.11.6078","article-title":"Cutting edge: IL-4 receptor expression by non-bone marrow-derived cells is required to expel gastrointestinal nematode parasites","volume":"167","author":"Urban","year":"2001","journal-title":"J. Immunol."},{"key":"2025032412152295600_r5","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1128\/IAI.69.5.2950-2956.2001","article-title":"Interleukin-4 is essential for the control of microfilariae in murine infection with the filaria Litomosoides sigmodontis","volume":"69","author":"Volkmann","year":"2001","journal-title":"Infect. Immun."},{"key":"2025032412152295600_r6","doi-asserted-by":"crossref","first-page":"4460","DOI":"10.1073\/pnas.85.12.4460","article-title":"Protective immunity and eosinophilia in IgE-deficient SJA\/9 mice infected with Nippostrongylus brasiliensis and Trichinella spiralis","volume":"85","author":"Watanabe","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032412152295600_r7","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1365-3024.1994.tb00333.x","article-title":"Expulsion of Hymenolepis nana from mice with congenital deficiencies of IgE production or of mast cell development","volume":"16","author":"Watanabe","year":"1994","journal-title":"Parasite Immunol."},{"key":"2025032412152295600_r8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nri2458","article-title":"Newly discovered roles for basophils: a neglected minority gains new respect","volume":"9","author":"Karasuyama","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"2025032412152295600_r9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/MOH.0b013e3282f13ce8","article-title":"Basophils and type 2 immunity","volume":"15","author":"Min","year":"2008","journal-title":"Curr. Opin. Hematol."},{"key":"2025032412152295600_r10","first-page":"141","article-title":"Basophils, basophilia and helminth infections","volume":"90","author":"Mitre","year":"2006","journal-title":"Chem. Immunol. Allergy"},{"key":"2025032412152295600_r11","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.immuni.2008.12.006","article-title":"Basophils: a nonredundant contributor to host immunity","volume":"30","author":"Sullivan","year":"2009","journal-title":"Immunity"},{"key":"2025032412152295600_r12","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.pt.2009.09.004","article-title":"The role of basophils in helminth infection","volume":"25","author":"Voehringer","year":"2009","journal-title":"Trends Parasitol."},{"key":"2025032412152295600_r13","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1007\/PL00000197","article-title":"Early IgE-dependent release of IL-4 and IL-13 from leukocytes is restricted to basophils: a comparison with other granulocytes and mononuclear cells","volume":"49","author":"Gibbs","year":"2000","journal-title":"Inflamm. Res."},{"key":"2025032412152295600_r14","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1073\/pnas.92.7.2534","article-title":"IgE receptor-positive non-B\/non-T cells dominate the production of interleukin 4 and interleukin 6 in immunized mice","volume":"92","author":"Aoki","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032412152295600_r15","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.4049\/jimmunol.172.4.2439","article-title":"Parasite antigen-driven basophils are a major source of IL-4 in human filarial infections","volume":"172","author":"Mitre","year":"2004","journal-title":"J. Immunol."},{"key":"2025032412152295600_r16","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1002\/1521-4141(200009)30:9<2660::AID-IMMU2660>3.0.CO;2-I","article-title":"MMCP-8, the first lineage-specific differentiation marker for mouse basophils. Elevated numbers of potent IL-4-producing and MMCP-8-positive cells in spleens of malaria-infected mice","volume":"30","author":"Poorafshar","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"2025032412152295600_r17","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.4049\/jimmunol.178.3.1396","article-title":"Induction of IL-4 expression in CD4(+) T cells by thymic stromal lymphopoietin","volume":"178","author":"Omori","year":"2007","journal-title":"J. Immunol."},{"key":"2025032412152295600_r18","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1146\/annurev.immunol.25.022106.141718","article-title":"TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation","volume":"25","author":"Liu","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"2025032412152295600_r19","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/365340a0","article-title":"Induction of human IgE synthesis in B cells by mast cells and basophils","volume":"365","author":"Gauchat","year":"1993","journal-title":"Nature"},{"key":"2025032412152295600_r20","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1046\/j.1365-2249.1998.00474.x","article-title":"Cultured basophils but not cultured mast cells induce human IgE synthesis in B cells after immunologic stimulation","volume":"111","author":"Yanagihara","year":"1998","journal-title":"Clin. Exp. Immunol."},{"key":"2025032412152295600_r21","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1182\/blood-2006-07-037739","article-title":"Induction of Th2 type immunity in a mouse system reveals a novel immunoregulatory role of basophils","volume":"109","author":"Oh","year":"2007","journal-title":"Blood"},{"key":"2025032412152295600_r22","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ni1558","article-title":"A mechanism for the initiation of allergen-induced T helper type 2 responses","volume":"9","author":"Sokol","year":"2008","journal-title":"Nat. Immunol."},{"key":"2025032412152295600_r23","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/ni.1740","article-title":"MHC class II-dependent basophil-CD4+ T cell interactions promote T(H)2 cytokine-dependent immunity","volume":"10","author":"Perrigoue","year":"2009","journal-title":"Nat. Immunol."},{"key":"2025032412152295600_r24","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1182\/blood-2007-01-068718","article-title":"Basophils are essential initiators of a novel type of chronic allergic inflammation","volume":"110","author":"Obata","year":"2007","journal-title":"Blood"},{"key":"2025032412152295600_r25","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1182\/blood-2008-05-154773","article-title":"Basophil effector function and homeostasis during helminth infection","volume":"113","author":"Ohnmacht","year":"2009","journal-title":"Blood"},{"key":"2025032412152295600_r26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.exppara.2009.05.009","article-title":"Litomosoides sigmodontis: a simple method to infect mice with L3 larvae obtained from the pleural space of recently infected jirds (Meriones unguiculatus)","volume":"123","author":"H\u00fcbner","year":"2009","journal-title":"Exp. Parasitol."},{"key":"2025032412152295600_r27","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/j.1365-2567.2008.02958.x","article-title":"Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells","volume":"127","author":"H\u00fcbner","year":"2009","journal-title":"Immunology"},{"key":"2025032412152295600_r28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0022-1759(00)00229-5","article-title":"A practical approach to multicolor flow cytometry for immunophenotyping","volume":"243","author":"Baumgarth","year":"2000","journal-title":"J. Immunol. Methods"},{"key":"2025032412152295600_r29","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1016\/j.vaccine.2009.12.016","article-title":"Type 2 immune-inducing helminth vaccination maintains protective efficacy in the setting of repeated parasite exposures","volume":"28","author":"H\u00fcbner","year":"2010","journal-title":"Vaccine"},{"key":"2025032412152295600_r30","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1365-2222.2008.03154.x","article-title":"CD200R surface expression as a marker of murine basophil activation","volume":"39","author":"Torrero","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"2025032412152295600_r31","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1046\/j.1365-3024.2001.00395.x","article-title":"Transmission intensity and human immune responses to lymphatic filariasis","volume":"23","author":"King","year":"2001","journal-title":"Parasite Immunol."},{"key":"2025032412152295600_r32","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1084\/jem.20040590","article-title":"Basophils produce IL-4 and accumulate in tissues after infection with a Th2-inducing parasite","volume":"200","author":"Min","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025032412152295600_r33","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1084\/jem.20052448","article-title":"Type 2 immunity is controlled by IL-4\/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system","volume":"203","author":"Voehringer","year":"2006","journal-title":"J. Exp. Med."},{"key":"2025032412152295600_r34","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1046\/j.1365-3024.1997.d01-209.x","article-title":"Immune response to the filaria Litomosoides sigmodontis in susceptible and resistant mice","volume":"19","author":"Mar\u00e9chal","year":"1997","journal-title":"Parasite Immunol."},{"key":"2025032412152295600_r35","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1046\/j.1365-3024.2001.00405.x","article-title":"Cellular immune responses of filaria (Litomosoides sigmodontis) infected BALB\/c mice detected on the level of cytokine transcription","volume":"23","author":"Taubert","year":"2001","journal-title":"Parasite Immunol."},{"key":"2025032412152295600_r36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00430-004-0226-1","article-title":"Increased early local immune responses and altered worm development in high-dose infections of mice susceptible to the filaria Litomosoides sigmodontis","volume":"194","author":"Babayan","year":"2005","journal-title":"Med. Microbiol. Immunol. (Berl.)"},{"key":"2025032412152295600_r37","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.ijpara.2006.04.008","article-title":"A time course study of immunological responses in Trichuris suis infected pigs demonstrates induction of a local type 2 response associated with worm burden","volume":"36","author":"Kringel","year":"2006","journal-title":"Int. J. Parasitol."},{"key":"2025032412152295600_r38","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0304-4017(91)90104-4","article-title":"Hematology and clinical pathology of experimental Fascioloides magna infection in cattle and guinea pigs","volume":"40","author":"Conboy","year":"1991","journal-title":"Vet. Parasitol."},{"key":"2025032412152295600_r39","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/j.jaci.2009.07.039","article-title":"Antigen-driven basophil activation is indicative of early Necator americanus infection in IgE-seronegative patients","volume":"124","author":"Falcone","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032412152295600_r40","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/0014-4894(78)90153-4","article-title":"Nippostrongylus brasiliensis: peripheral blood leucocyte response of rats, with special reference to basophils","volume":"46","author":"Ogilvie","year":"1978","journal-title":"Exp. Parasitol."},{"key":"2025032412152295600_r41","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/j.0141-9838.2004.00724.x","article-title":"Echinococcus multilocularis metacestode extract triggers human basophils to release interleukin-4","volume":"26","author":"Aum\u00fcller","year":"2004","journal-title":"Parasite Immunol."},{"key":"2025032412152295600_r42","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1189\/jlb.0702356","article-title":"Basophils express a type 2 cytokine profile on exposure to proteases from helminths and house dust mites","volume":"73","author":"Phillips","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"2025032412152295600_r43","doi-asserted-by":"crossref","first-page":"6023","DOI":"10.4049\/jimmunol.178.10.6023","article-title":"Cutting edge: IPSE\/alpha-1, a glycoprotein from Schistosoma mansoni eggs, induces IgE-dependent, antigen-independent IL-4 production by murine basophils in vivo","volume":"178","author":"Schramm","year":"2007","journal-title":"J. Immunol."},{"key":"2025032412152295600_r44","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/32190","article-title":"Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites","volume":"392","author":"Lantz","year":"1998","journal-title":"Nature"},{"key":"2025032412152295600_r45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00430-002-0155-9","article-title":"Murine filariasis: interleukin 4 and interleukin 5 lead to containment of different worm developmental stages","volume":"192","author":"Volkmann","year":"2003","journal-title":"Med. Microbiol. Immunol. (Berl.)"},{"key":"2025032412152295600_r46","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.jaci.2005.12.1341","article-title":"IgE memory: Persistence of antigen-specific IgE responses years after treatment of human filarial infections","volume":"117","author":"Mitre","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032412152295600_r47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molbiopara.2009.04.008","article-title":"Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity","volume":"167","author":"Hewitson","year":"2009","journal-title":"Mol. Biochem. Parasitol."},{"key":"2025032412152295600_r48","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1365-3024.2005.00792.x","article-title":"Immunomodulation by filarial nematodes","volume":"27","author":"Hoerauf","year":"2005","journal-title":"Parasite Immunol."},{"key":"2025032412152295600_r49","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.0105-2896.2004.00191.x","article-title":"Helminth parasites\u2014masters of regulation","volume":"201","author":"Maizels","year":"2004","journal-title":"Immunol. Rev."},{"key":"2025032412152295600_r50","doi-asserted-by":"crossref","first-page":"4924","DOI":"10.4049\/jimmunol.174.8.4924","article-title":"Removal of regulatory T cell activity reverses hyporesponsiveness and leads to filarial parasite clearance in vivo","volume":"174","author":"Taylor","year":"2005","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/185\/12\/7426\/61652765\/0903864.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/185\/12\/7426\/61652765\/0903864.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T23:42:46Z","timestamp":1743205366000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/185\/12\/7426\/7984546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12]]},"references-count":50,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2010,12,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0903864","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.6231956.6302054","asserted-by":"object"}]},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,12]]},"published":{"date-parts":[[2010,12]]}}}