T and B cells are not required for clearing Staphylococcus aureus in systemic infection despite a strong TLR2-MyD88-dependent T cell activation

• Published in: The Journal of immunology (1950) Vol. 186; no. 1; pp. 443 - 452
• Main Authors: Schmaler, Mathias, Jann, Naja J, Ferracin, Fabrizia, Landmann, Regine
• Format: Journal Article
• Language: English
• Published: United States 01.01.2011
• Subjects: Animals; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - microbiology; Cell Differentiation - immunology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - microbiology; Immunity, Innate; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Interleukin-17 - biosynthesis; Lipoproteins - physiology; Lymphocyte Activation - immunology; Mice; Myeloid Differentiation Factor 88 - physiology; Signal Transduction - immunology; Staphylococcal Infections - immunology; Staphylococcal Infections - metabolism; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - growth & development; Staphylococcus aureus - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - microbiology; Toll-Like Receptor 2 - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1001407

Staphylococcus aureus infection elicits through its mature lipoproteins an innate immune response by TLR2-MyD88 signaling, which improves bacterial clearing and disease outcome. The role of dendritic cells (DCs) and T cells in this immune activation and the function of T and B cells in defense against S. aureus infection remain unclear. Therefore, we first evaluated DC and T cell activation after infection with S. aureus wild type (WT) and its isogenic mutant, which is deficient in lipoprotein maturation, in vitro. Lipoproteins in viable S. aureus contributed via TLR2-MyD88 to activation of DCs, which promoted the release of IFN-γ and IL-17 in CD4(+) T cells. This strong effect was independent of superantigens and MHC class II. We next evaluated the function of T cells and their cytokines IFN-γ and IL-17 in infection in vivo. Six days after systemic murine infection IFN-γ, IL-17, and IL-10 production in total spleen cells were MyD88-dependent and their levels increased until day 21. The comparison of CD3(-/-), Rag2(-/-), and C57BL/6 mice after infection revealed that IFN-γ and IL-17 originated from T cells and IL-10 originated from innate immune cells. Furthermore, vaccination of mice to activate T and B cells did not improve eradication of S. aureus from organs. In conclusion, S. aureus enhances DC activation via TLR2-MyD88 and thereby promotes T(H)1 and T(H)17 cell differentiation. However, neither T cells and their MyD88-regulated products, IFN-γ and IL-17, nor B cells affected bacterial clearing from organs and disease outcome.