{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T22:14:44Z","timestamp":1757542484847},"reference-count":27,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2006,10,1]],"date-time":"2006-10-01T00:00:00Z","timestamp":1159660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Infection with<jats:italic>Borrelia burgdorferi<\/jats:italic>, the causative agent of Lyme disease, results in a Th1 response and proinflammatory cytokine production. Mice deficient for MKK3, an upstream activator of p38 mitogen-activated protein (MAP) kinase, develop a lower Th1 response and exhibit an impaired ability to produce proinflammatory cytokines upon infection with the spirochete. We investigated the contribution of p38 MAP kinase activity in gamma interferon (IFN-\u03b3) production in CD4<jats:sup>+<\/jats:sup>T cells in response to specific antigen through T-cell receptor (TCR)- and interleukin-12 (IL-12)-mediated signals. The specific inhibition of p38 MAP kinase in T cells and the administration of a pharmacological inhibitor of the kinase during the course of infection with the spirochete resulted in reduced levels of IFN-\u03b3 in the sera of infected mice. Our results also demonstrate that although p38 MAP kinase activity is not required for the differentiation of<jats:italic>B. burgdorferi<\/jats:italic>-specific CD4<jats:sup>+<\/jats:sup>T cells, the production of IFN-\u03b3 by Th1 effector cells is regulated by the kinase. Both TCR engagement and IL-12 induced the production of the Th1 cytokine through the activation of the p38 MAP kinase pathway. Thus, the inhibition of this pathway in vitro resulted in decreased levels of IFN-\u03b3 during restimulation of<jats:italic>B. burgdorferi<\/jats:italic>-specific T cells in response to anti-CD3 and IL-12 stimulation. These results clarify the specific contribution of the p38 MAP kinase in the overall immune response to the spirochete and its role in the effector function of<jats:italic>B. burgdorferi<\/jats:italic>-specific T cells.<\/jats:p>","DOI":"10.1128\/iai.00623-06","type":"journal-article","created":{"date-parts":[[2006,9,20]],"date-time":"2006-09-20T23:06:35Z","timestamp":1158793595000},"page":"5713-5717","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Control of<i>Borrelia burgdorferi<\/i>-Specific CD4<sup>+<\/sup>-T-Cell Effector Function by Interleukin-12- and T-Cell Receptor-Induced p38 Mitogen-Activated Protein Kinase Activity"],"prefix":"10.1128","volume":"74","author":[{"given":"Michael N.","family":"Hedrick","sequence":"first","affiliation":[{"name":"Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Chris M.","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietrich B.","family":"Conze","sequence":"additional","affiliation":[{"name":"Immunobiology Program, Department of Internal Medicine, University of Vermont College of Medicine, Burlington, Vermont 05405"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tonya C.","family":"Bates","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223"},{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Rinco\u0301n","sequence":"additional","affiliation":[{"name":"Immunobiology Program, Department of Internal Medicine, University of Vermont College of Medicine, Burlington, Vermont 05405"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Anguita","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223"},{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.12.6352"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-6445(03)00036-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118494"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.6.3383"},{"key":"e_1_3_2_6_2","first-page":"1453","volume":"279","year":"1996","unstructured":"Badger, A. 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