title: Toll-like receptor 9 is required for full host resistance to Mycobacterium avium infection but plays no role in induction of Th1 responses.
abstract: To investigate the role of Toll-like receptor 9 (TLR9) in innate immunity to Mycobacterium avium, TLR9, TLR2, and MyD88 knockout (KO) mice were infected with this bacterium. Bacterial burdens were higher in the spleens, livers, and lungs of infected TLR9 KO mice than in those of C57BL/6 mice, indicating that TLR9 is required for efficient control of M. avium infection. However, TLR9 KO or TLR2 KO spleen cells displayed normal M. avium-induced tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) responses. This finding was confirmed by determining the number of splenic CD4(+) T cells producing IFN-γ by flow cytometry. Furthermore, TLR2 and MyD88, but not TLR9, played a major role in interleukin-12 and TNF-α production by M. avium-infected macrophages and dendritic cells (DCs). We also found that major histocompatibility complex class II molecule expression on DCs is regulated by TLR2 and MyD88 signaling but not by TLR9. Finally, lack of TLR9, TLR2, or MyD88 reduced the numbers of macrophages, epithelioid cells, and lymphocytes in M. avium-induced granulomas but only MyD88 deficiency affected the number of liver granulomas. In summary, our data demonstrated that the involvement of TLR9 in the control of M. avium infection is not related to the induction of Th1 responses.
authors.affiliation: Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Natália B
authors.initials: NB
authors.lastname: Carvalho
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Oliveira
authors.forename: Fernanda V
authors.initials: FV
authors.lastname: Durães
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: de Almeida
authors.forename: Manuela
authors.initials: M
authors.lastname: Flórido
authors.forename: Luana O
authors.initials: LO
authors.lastname: Prata
authors.forename: Marcelo V
authors.initials: MV
authors.lastname: Caliari
authors.forename: Rui
authors.initials: R
authors.lastname: Appelberg
authors.forename: Sérgio C
authors.initials: SC
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009162:Mycobacterium avium / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology / Q000662:veterinary
chemical_list: D000949:Histocompatibility Antigens Class II; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9