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Innate immune responses to Rhodococcus equi.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 Aug 01; Vol. 173 (3), pp. 1914-24. - Publication Year :
- 2004
-
Abstract
- We examined innate immune responses to the intracellular bacterium Rhodococcus equi and show that infection of macrophages with intact bacteria induced the rapid translocation of NF-kappa B and the production of a variety of proinflammatory mediators, including TNF, IL-12, and NO. Macrophages from mice deficient in MyD88 failed to translocate NF-kappa B and produced virtually no cytokines in response to R. equi infection, implicating a TLR pathway. TLR4 was not involved in this response, because C3H/HeJ macrophages were fully capable of responding to R. equi infection, and because RAW-264 cells transfected with a dominant negative form of TLR4 responded normally to infection by R. equi. A central role for TLR2 was identified. A TLR2 reporter cell was activated by R. equi, and RAW-264 cells transfected with a dominant negative TLR2 exhibited markedly reduced cytokine responses to R. equi. Moreover, macrophages from TLR2(-/-) mice exhibited diminished cytokine responses to R. equi. The role of the surface-localized R. equi lipoprotein VapA (virulence-associated protein A), in TLR2 activation was examined. Purified rVapA activated a TLR2-specific reporter cell, and it induced the maturation of dendritic cells and the production of cytokines from macrophages. Importantly, TLR2(-/-)-deficient but not TLR4(-/-)-deficient mice were found to be compromised in their ability to clear a challenge with virulent R. equi. We conclude that the efficient activation of innate immunity by R. equi may account for the relative lack of virulence of this organism in immunocompetent adults.
- Subjects :
- Adaptor Proteins, Signal Transducing
Animals
Antigens, Differentiation genetics
Bacterial Proteins immunology
Bacterial Proteins physiology
CHO Cells
Cricetinae
Dendritic Cells immunology
Female
Immunity, Innate
Immunocompetence
Interleukin-12 biosynthesis
Interleukin-12 genetics
Macrophages immunology
Macrophages metabolism
Membrane Glycoproteins deficiency
Membrane Glycoproteins genetics
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
NF-kappa B metabolism
Nitric Oxide biosynthesis
Receptors, Cell Surface deficiency
Receptors, Cell Surface genetics
Receptors, Immunologic deficiency
Receptors, Immunologic genetics
Recombinant Fusion Proteins physiology
Rhodococcus equi pathogenicity
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptors
Transfection
Tumor Necrosis Factor-alpha biosynthesis
Tumor Necrosis Factor-alpha genetics
Virulence
Virulence Factors immunology
Virulence Factors physiology
Membrane Glycoproteins physiology
Receptors, Cell Surface physiology
Rhodococcus equi immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 173
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15265925
- Full Text :
- https://doi.org/10.4049/jimmunol.173.3.1914