{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:07:12Z","timestamp":1761919632654},"reference-count":55,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"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":[[2012,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Interleukin-1 receptor (IL1R)-associated kinase 4 (IRAK4) is a member of the IRAK family and has an important role in inducing the production of inflammatory mediators. This kinase is downstream of MyD88, an adaptor protein essential for Toll-like receptor (TLR) function. We investigated the role of this kinase in IRAK4-deficient mice orally infected with the cystogenic ME49 strain of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma gondii<\/jats:named-content>. IRAK4<jats:sup>\u2212\/\u2212<\/jats:sup>mice displayed higher morbidity, tissue parasitism, and accelerated mortality than the control mice. The lymphoid follicles and germinal centers from infected IRAK4<jats:sup>\u2212\/\u2212<\/jats:sup>mice were significantly smaller. We consistently found that IRAK4<jats:sup>\u2212\/\u2212<\/jats:sup>mice showed a defect in splenic B cell activation and expansion as well as diminished production of gamma interferon (IFN-\u03b3) by T lymphocytes. The myeloid compartment was also affected. Both the frequency and ability of dendritic cells (DCs) and monocytes\/macrophages to produce IL-12 were significantly decreased, and resistance to infection with<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma<\/jats:named-content>was rescued by treating IRAK4<jats:sup>\u2212\/\u2212<\/jats:sup>mice with recombinant IL-12 (rIL-12). Additionally, we report the association of IRAK4 haplotype-tagging single nucleotide polymorphisms (tag-SNPs) with congenital toxoplasmosis in infected individuals (rs1461567 and rs4251513,<jats:italic>P<\/jats:italic>&lt; 0.023 and<jats:italic>P<\/jats:italic>&lt; 0.045, respectively). Thus, signaling via IRAK4 is essential for the activation of innate immune cells, development of parasite-specific acquired immunity, and host resistance to infection with<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. gondii<\/jats:named-content>.<\/jats:p>","DOI":"10.1128\/iai.00328-12","type":"journal-article","created":{"date-parts":[[2012,10,2]],"date-time":"2012-10-02T06:04:49Z","timestamp":1349157889000},"page":"4298-4308","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Impaired Innate Immunity in Mice Deficient in Interleukin-1 Receptor-Associated Kinase 4 Leads to Defective Type 1 T Cell Responses, B Cell Expansion, and Enhanced Susceptibility to Infection with Toxoplasma gondii"],"prefix":"10.1128","volume":"80","author":[{"given":"Samantha R.","family":"B\u00e9la","sequence":"first","affiliation":[{"name":"Centro de Pesquisas Ren\u00e9 Rachou, CPqRR\u2013Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, Brazil"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00edriam S.","family":"Dutra","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Ren\u00e9 Rachou, CPqRR\u2013Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, Brazil"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernest","family":"Mui","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Ophthalmology and Pediatrics (Infectious Disease), University of Chicago, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Montpetit","sequence":"additional","affiliation":[{"name":"McGill University and G\u00e9nome Qu\u00e9bec Innovation Center, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda S.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9rgio C.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa M. E.","family":"Arantes","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lis R.","family":"Antonelli","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Ren\u00e9 Rachou, CPqRR\u2013Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rima","family":"McLeod","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Ophthalmology and Pediatrics (Infectious Disease), University of Chicago, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo T.","family":"Gazzinelli","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Ren\u00e9 Rachou, CPqRR\u2013Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, Brazil"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"},{"name":"University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40817"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1379\/CSC-138R.1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.5.1995-2001.1994"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5252.1128"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.12.012"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1128346"},{"key":"e_1_3_2_8_2","first-page":"1017","article-title":"Involvement of MyD88 in host defense and the down-regulation of anti-heat shock protein 70 autoantibody formation by MyD88 in Toxoplasma gondii-infected mice","volume":"88","author":"Chen M","year":"2002","unstructured":"ChenM. 2002. 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