{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:06:29Z","timestamp":1790762789739,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T00:00:00Z","timestamp":1141171200000},"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":[[2006,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Patent lymphatic filariasis is characterized by a profound down-regulation of immune responses with both parasite Ag-specific tolerance and bystander suppression. Although this down-regulation is confined to the Th1 arm of the immune system in response to parasite Ag, we hypothesized a more generalized suppression in response to live parasites. Indeed, when we examined the cytokine profile of a cohort of filaria-infected (n = 10) and uninfected (n = 10) individuals in response to live infective-stage larvae or microfilariae of Brugia malayi, we found significant impairment of both Th1 and Th2 cytokines characterized by diminished production of IFN-\u03b3, TNF-\u03b1, IL-4, IL-5, and IL-10 in infected patients. The molecular basis of this impaired Th1\/Th2 response was examined, and we identified three major networks of immunoregulation and tolerance. First, impaired induction of T-bet and GATA-3 mRNA underlies the Th1\/Th2 deficiency in infected individuals. Second, regulatory networks, as evidenced by significantly increased expression of Foxp3 (natural regulatory T cell marker) and regulatory effectors such as TGF-\u03b2, CTLA-4, PD-1, ICOS, and indoleamine 2,3-dioxygenase play an important role in immunosuppression. Third, the compromise of effector T cell function is mediated by the enhanced induction of anergy-inducing factors cbl-b, c-cbl (cbl is abbreviation for Casitas B lymphoma), Itch, and Nedd4. Indeed, blocking CTLA-4 or neutralizing TGF-\u03b2 restored the ability to mount Th1\/Th2 responses to live parasites and reversed the induction of anergy-inducing factors. Hence, we conclude that a profound impairment of live parasite-specific Th1 and Th2 immune responses occurs in lymphatic filariasis that is governed at the transcriptional level by a complex interplay of inhibitory mediators.<\/jats:p>","DOI":"10.4049\/jimmunol.176.5.3248","type":"journal-article","created":{"date-parts":[[2014,4,23]],"date-time":"2014-04-23T19:49:01Z","timestamp":1398282541000},"page":"3248-3256","source":"Crossref","is-referenced-by-count":195,"title":["Regulatory Networks Induced by Live Parasites Impair Both Th1 and Th2 Pathways in Patent Lymphatic Filariasis: Implications for Parasite Persistence"],"prefix":"10.1093","volume":"176","author":[{"given":"Subash","family":"Babu","sequence":"first","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla P","family":"Blauvelt","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Kumaraswami","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Center , Chennai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B","family":"Nutman","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,3,1]]},"reference":[{"key":"2026020211401019900_R1","first-page":"15","volume-title":"Ciba Found. 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