title: Nucleotide-binding oligomerization domain-2 (NOD2) regulates type-1 cytokine responses to Mycobacterium avium but is not required for host control of infection.
abstract: Nucleotide-binding oligomerization domain-2 (NOD2) is an innate immune receptor that recognizes peptidoglycan-derived muramyl dipeptide from intracellular bacteria and triggers proinflammatory signals. In this study, we sought to evaluate the role played by this receptor during early and late stages of infection with Mycobacterium avium in mice. We demonstrated that NOD2 knockout (KO) animals were able to control M. avium infection similarly to wild-type mice at all time points studied, even though IL-12 and TNF-α production was impaired in NOD2-deficient macrophages. At 100 days following infection with this bacterium, but not at 30 days post-infection, NOD2-deficient mice showed significantly diminished production of IFN-γ, as confirmed by reduced accumulation of IFN-γ and IL-12 mRNA in the spleens of KO mice. Additionally, a reduction in the size and in the number of lymphocytes/granulocytes of hepatic granulomas from NOD2 KO animals was observed only during late time points of M. avium infection. Taken together, these data demonstrate that NOD2 regulates type-1 cytokine responses to M. avium but is not required for the control of infection with this bacterium in vivo.
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Natália B
authors: NB
authors: Carvalho
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Fernanda S
authors: FS
authors: Oliveira
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Fábio A V
authors: FA
authors: Marinho
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Leonardo A
authors: LA
authors: de Almeida
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Júlia S
authors: JS
authors: Fahel
authors: Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors: André
authors: A
authors: Báfica
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors: Antonio G
authors: AG
authors: Rothfuchs
authors: Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, FMRP/USP, Ribeirão Preto, São Paulo, Brazil.
authors: Dario S
authors: DS
authors: Zamboni
authors: Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Marcelo V
authors: MV
authors: Caliari
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: scozeus@icb.ufmg.br.
authors: Sérgio C
authors: SC
authors: Oliveira
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D007239:Infections / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009162:Mycobacterium avium / Q000166:cytology / Q000502:physiology*; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D011971:Receptors, Immunologic
keywords: Cytosolic sensor; Innate immunity receptor; Mycobacterium avium; NOD2