{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:43:58Z","timestamp":1761155038596,"version":"3.37.3"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2007,1,22]],"date-time":"2007-01-22T00:00:00Z","timestamp":1169424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 AI47189","RO1 A1 22662"],"award-info":[{"award-number":["RO1 AI47189","RO1 A1 22662"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007048","name":"Mayo Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The heterotrimeric guanine nucleotide-binding protein G\u03b1i2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. G\u03b1i2\u2212\/\u2212 mice have a selectively impaired IgM response consistent with a disorder in B cell development yet have augmented T cell effector function associated with increased production of IFN-\u03b3 and IL-4. The goal of the present study was to determine if a deficiency in the G\u03b1i2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL-4-, IL-5-, and IgM-dependent. G\u03b1i2\u2212\/\u2212 and wild-type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses against infection. G\u03b1i2\u2212\/\u2212 mice failed to kill the larvae in the challenge infection as compared with wild-type mice despite developing an antigen-specific Th2 response characterized by increased IL-4, IL-5, IgM, and IgG. Transfer of serum collected from immunized G\u03b1i2\u2212\/\u2212 mice to na\u00efve wild-type mice conferred passive protective immunity against S. stercoralis infection thus confirming the development of a protective antibody response in G\u03b1i2\u2212\/\u2212 mice. Differential cell analyses and myeloperoxidase assays for quantification of neutrophils showed a significantly reduced recruitment of neutrophils into the microenvironment of the parasites in immunized G\u03b1i2\u2212\/\u2212 mice. However, cell transfer studies demonstrated that neutrophils from G\u03b1i2\u2212\/\u2212 mice are competent in killing larvae. These data demonstrate that G\u03b1i2 signaling events are not required for the development of the protective immune responses against S. stercoralis; however, G\u03b1i2 is essential for the recruitment of neutrophils required for host-dependent killing of larvae.<\/jats:p>","DOI":"10.1189\/jlb.1106695","type":"journal-article","created":{"date-parts":[[2007,1,23]],"date-time":"2007-01-23T01:58:30Z","timestamp":1169517510000},"page":"1120-1126","source":"Crossref","is-referenced-by-count":18,"title":["Signaling through G\u03b1i2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larval<i>Strongyloides stercoralis<\/i>in mice"],"prefix":"10.1093","volume":"81","author":[{"given":"Udaikumar M","family":"Padigel","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Thomas Jefferson University , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Thomas Jefferson University , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Redding","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Thomas Jefferson University , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James J","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic , Scottsdale, Arizona , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J","family":"Nolan","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard A","family":"Schad","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lutz","family":"Birnbaumer","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health Sciences (NIEHS), Laboratory of Signal Transduction, Research Triangle Park , North Carolina , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Abraham","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Thomas Jefferson University , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,1,22]]},"reference":[{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1084\/jem.191.9.1605","article-title":"Primary role for Gi protein signaling in the regulation of interleukin 12 production and the induction of T helper cell type 1 responses","volume":"191","author":"He","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1093\/intimm\/dxg135","article-title":"TCR-mediated hyper-responsiveness of autoimmune G\u03b1i2(\u2013\/\u2013) mice is an intrinsic naive CD4(+) T cell disorder selective for the G\u03b1i2 subunit","volume":"15","author":"Huang","year":"2003","journal-title":"Int. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev.iy.12.040194.003113","article-title":"The molecular biology of leukocyte chemoattractant receptors","volume":"12","author":"Murphy","year":"1994","journal-title":"Annu. Rev. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/intimm\/10.5.651","article-title":"Pertussis toxin potentiates Th1 and Th2 responses to co-injected antigen: adjuvant action is associated with enhanced regulatory cytokine production and expression of the co-stimulatory molecules B7\u20131, B7\u20132 and CD28","volume":"10","author":"Ryan","year":"1998","journal-title":"Int. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3109\/10799899509045218","article-title":"Signal transduction by G proteins: 1994 edition","volume":"15","author":"Birnbaumer","year":"1995","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"101S","DOI":"10.1007\/BF01540899","article-title":"Gi2 \u03b1 protein deficiency: a model of inflammatory bowel disease","volume":"15","author":"Rudolph","year":"1995","journal-title":"J. Clin. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.4049\/jimmunol.158.3.1068","article-title":"G(\u03b1)i2-deficient mice with colitis exhibit a local increase in memory CD4+ T cells and proinflammatory Th1-type cytokines","volume":"158","author":"Hornquist","year":"1997","journal-title":"J. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.4049\/jimmunol.170.4.1707","article-title":"B cell developmental requirement for the G \u03b1 i2 gene","volume":"170","author":"Dalwadi","year":"2003","journal-title":"J. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.4049\/jimmunol.170.4.1728","article-title":"Pertussis toxin enhances Th1 responses by stimulation of dendritic cells","volume":"170","author":"Hou","year":"2003","journal-title":"J. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1136\/gut.51.3.392","article-title":"Regression of Peyer\u2019s patches in G \u03b1 i2 deficient mice prior to colitis is associated with reduced expression of Bcl-2 and increased apoptosis","volume":"51","author":"Ohman","year":"2002","journal-title":"Gut"},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1046\/j.1365-3083.2000.00759.x","article-title":"Immune activation in the intestinal mucosa before the onset of colitis in G\u03b1i2-deficient mice","volume":"52","author":"Ohman","year":"2000","journal-title":"Scand. J. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1128\/iai.61.7.2834-2840.1993","article-title":"Enhancement of interleukin-4 production by pertussis toxin","volume":"61","author":"Mu","year":"1993","journal-title":"Infect. Immun."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/0008-8749(86)90394-1","article-title":"Pertussigen enhances antigen-driven interferon-\u03b3 production by sensitized lymphoid cells","volume":"97","author":"Sewell","year":"1986","journal-title":"Cell. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"497","DOI":"10.4049\/jimmunol.159.1.497","article-title":"Triggers of autoimmune disease in a murine TCR-transgenic model for multiple sclerosis","volume":"159","author":"Brabb","year":"1997","journal-title":"J. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0090-1229(86)90096-6","article-title":"The effects of pertussis toxin on the induction and transfer of experimental autoimmune uveoretinitis","volume":"39","author":"McAllister","year":"1986","journal-title":"Clin. Immunol. Immunopathol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.4049\/jimmunol.165.8.4544","article-title":"Role of IL-5 in innate and adaptive immunity to larval Strongyloides stercoralis in mice","volume":"165","author":"Herbert","year":"2000","journal-title":"J. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1046\/j.0141-9838.2001.00441.x","article-title":"The role of B cells in immunity against larval Strongyloides stercoralis in mice","volume":"24","author":"Herbert","year":"2002","journal-title":"Parasite Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1006\/expr.1996.0035","article-title":"Strongyloides stercoralis: role of antibody and complement in immunity to the third stage of larvae in BALB\/cByJ mice","volume":"82","author":"Brigandi","year":"1996","journal-title":"Exp. Parasitol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1046\/j.1365-3024.1997.d01-142.x","article-title":"IL-12 eliminates the Th-2 dependent protective immune response of mice to larval","volume":"19","author":"Rotman","year":"1997","journal-title":"Strongyloides stercoralis. Parasite Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.4049\/jimmunol.176.7.4315","article-title":"Complement component C3 is required for protective innate and adaptive immunity to larval Strongyloides stercoralis in mice","volume":"176","author":"Kerepesi","year":"2006","journal-title":"J. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"5730","DOI":"10.1128\/IAI.01958-05","article-title":"Role of eosinophils and neutrophils in innate and adaptive protective immunity to larval Strongyloides stercoralis in mice","volume":"74","author":"Galioto","year":"2006","journal-title":"Infect. Immun."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/jlb.67.5.742","article-title":"Positive regulation of human T cell activation by Gi2 proteins and interleukin-8","volume":"67","author":"Lippert","year":"2000","journal-title":"J. Leukoc. Biol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/01.shk.0000129759.58490.d6","article-title":"Toll-like receptor 4 coupled GI protein signaling pathways regulate extracellular signal-regulated kinase phosphorylation and AP-1 activation independent of NF\u03baB activation","volume":"22","author":"Fan","year":"2004","journal-title":"Shock"},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.micinf.2006.10.003","article-title":"Toll-like receptor 4 (TLR4) is required for protective immunity to larval Strongyloides stercoralis in mice","volume":"9","author":"Kerepesi","year":"2007","journal-title":"Microbes Infect."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1006\/expr.1995.1036","article-title":"Strongyloides stercoralis: protective immunity to third-stage larvae inBALB\/cByJ mice","volume":"80","author":"Abraham","year":"1995","journal-title":"Exp. Parasitol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0014-4894(02)00008-5","article-title":"Immunoaffinity-isolated antigens induce protective immunity against larval Strongyloides stercoralis in mice","volume":"100","author":"Herbert","year":"2002","journal-title":"Exp. Parasitol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1083\/jcb.133.4.895","article-title":"Deficiency of Src family kinases p59\/61hck and p58c-fgr results in defective adhesion-dependent neutrophil functions","volume":"133","author":"Lowell","year":"1996","journal-title":"J. Cell Biol."},{"key":"2023033007020300300_","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":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.0105-2896.2004.00187.x","article-title":"Th2 response polarization during infection with the helminth parasite","volume":"201","author":"Pearce","year":"2004","journal-title":"Schistosoma mansoni. Immunol. Rev."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.4049\/jimmunol.153.3.1216","article-title":"Adult and microfilarial stages of the filarial parasite Brugia malayi stimulate contrasting cytokine and Ig isotype responses in BALB\/c mice","volume":"153","author":"Lawrence","year":"1994","journal-title":"J. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1084\/jem.173.1.159","article-title":"Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth","volume":"173","author":"Pearce","year":"1991","journal-title":"Schistosoma mansoni. J. Exp. Med."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"6835","DOI":"10.1128\/IAI.71.12.6835-6843.2003","article-title":"Specificity and mechanism of immunoglobulin M (IgM)- and IgG-dependent protective immunity to larval Strongyloides stercoralis in mice","volume":"71","author":"Ligas","year":"2003","journal-title":"Infect. Immun."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/ng0695-143","article-title":"Ulcerative colitis and adenocarcinoma of the colon in G \u03b1 i2-deficient mice","volume":"10","author":"Rudolph","year":"1995","journal-title":"Nat. Genet."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1128\/IAI.69.6.4007-4018.2001","article-title":"Ascaris suum-derived products induce human neutrophil activation via a G protein-coupled receptor that interacts with the interleukin-8 receptor pathway","volume":"69","author":"Falcone","year":"2001","journal-title":"Infect. Immun."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1084\/jem.182.2.581","article-title":"Pertussis toxin inhibits migration of B and T lymphocytes into splenic white pulp cords","volume":"182","author":"Cyster","year":"1995","journal-title":"J. Exp. Med."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.4049\/jimmunol.135.6.4135","article-title":"Inhibition of lymphocyte and neutrophil chemotaxis by pertussis toxin","volume":"135","author":"Spangrude","year":"1985","journal-title":"J. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"250","DOI":"10.4049\/jimmunol.167.1.250","article-title":"Pertussis toxin inhibits induction of tissue-specific autoimmune disease by disrupting G protein-coupled signals","volume":"167","author":"Su","year":"2001","journal-title":"J. Immunol."},{"key":"2023033007020300300_","doi-asserted-by":"crossref","first-page":"C293","DOI":"10.1152\/ajpcell.00394.2004","article-title":"Lipopolysaccharide- and gram-positive bacteria-induced cellular inflammatory responses: role of heterotrimeric G\u03b1(i) proteins","volume":"289","author":"Fan","year":"2005","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2023033007020300300_","article-title":"Extravasation of leukocytes from circulation is controlled by G\u03b1i2 signaling events in the endothelium","author":"Pero","year":"2006","journal-title":"Proc. Natl. Acad. Sci."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1189%2Fjlb.1106695","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/81\/4\/1120\/49638958\/jlb1120.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/81\/4\/1120\/49638958\/jlb1120.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T10:49:28Z","timestamp":1707562168000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/81\/4\/1120\/6975645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1,22]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2007,1,22]]},"published-print":{"date-parts":[[2007,4,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.1106695","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"type":"print","value":"0741-5400"},{"type":"electronic","value":"1938-3673"}],"subject":[],"published-other":{"date-parts":[[2007,4]]},"published":{"date-parts":[[2007,1,22]]}}}