| Author | Béla, Samantha Ribeiro | |
| Author | Dutra, Miriam Santos | |
| Author | Mui, Ernest J. | |
| Author | Montpetit, Alexandre | |
| Author | Oliveira, Fernanda S. | |
| Author | Paula, Sergio Oliveira de | |
| Author | Arantes, Rosa Maria Esteves | |
| Author | Antonelli, Lis Ribeiro do Valle | |
| Author | McLeod, Rima | |
| Author | Gazzinelli, Ricardo Tostes | |
| Access date | 2014-02-28T15:57:16Z | |
| Available date | 2014-02-28T15:57:16Z | |
| Document date | 2012 | |
| Citation | BELA, Samantha Ribeiro et al. 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. Infection and Immunity. 2012, vol.80, pp. 4298-4308 | pt_BR |
| ISSN | 0019-9567 | |
| URI | https://www.arca.fiocruz.br/handle/icict/7375 | |
| Language | eng | pt_BR |
| Publisher | American Society for Microbiology | pt_BR |
| Rights | open access | pt_BR |
| 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 | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1128/IAI.00328-12 | |
| Abstract | Interleukin-1 receptor (IL1R)-associated kinase 4 (IRAK4) is a member of the IRAK family and has an important role in induc-ing 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 Toxoplasma gondii. IRAK4/mice displayed higher morbidity, tissue parasitism, and accelerated mortality than the control mice. The lymphoid follicles and germinal centers from infected IRAK4/ mice were significantly smaller. We consistently found that IRAK4/mice showed a defect in splenic B cell activation and expansion as well as diminished production of gamma interferon (IFN-) 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 Toxoplasma was rescued by treating IRAK4/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, P< 0.023 and P<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 T. gondii. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | University of Chicago. Departments of Surgery, Ophthalmology and Pediatrics (Infectious Disease). Chicago, Illinois, USA | pt_BR |
| Affilliation | McGill University and Génome Québec Innovation Center. Montréal, Québec, Canada | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | University of Chicago. Departments of Surgery, Ophthalmology and Pediatrics (Infectious Disease). Chicago, Illinois, USA | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil/University of Massachusetts Medical School. Worcester, MA, USA | pt_BR |
| Subject | Toxoplasma gondii | pt_BR |
| Subject | immunity | pt_BR |
