T and B Cells Are Not Required for ClearingStaphylococcus aureusin Systemic Infection Despite a Strong TLR2–MyD88-Dependent T Cell Activation

Abstract

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 TH1 and TH17 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.

BDCA1-Positive Dendritic Cells (DCs) Represent a Unique Human Myeloid DC Subset That Induces Innate and Adaptive Immune Responses to Staphylococcus aureus Infection

“…To further clarify the mechanism by which S. aureus promotes maturation of DCs, we examined the role of the MyD88 signaling pathway, a critical pathway activated by TLR stimulation in innate immune cells (21). It has also been reported that MyD88 is required for TLR signal transduction in mouse DCs in response to S. aureus (22,23). Therefore, we assessed whether the activation of human blood BDCA1 ϩ mDCs by S. aureus is dependent on the MyD88 signaling pathway.…”

Protective Immunity against Recurrent Staphylococcus aureus Skin Infection Requires Antibody and Interleukin-17A

“…The results of one representative experiment are presented; each was repeated at least once. mutant S. aureus strains but not wild-type isolates elicit adaptive immunity against S. aureus sepsis in single strains of mice (19)(20)(21)(22). Therefore, our model, in which a natural SSTI with a wild-type S. aureus clinical isolate elicited protective immunity in BALB/c but not C57BL/6 mice, afforded us a unique opportunity to dissect the determinants of protection against recurrent infection.…”

The Loss of RGS Protein-Gαi2 Interactions Results in Markedly Impaired Mouse Neutrophil Trafficking to Inflammatory Sites

“…However, C57BL/6 mice become completely susceptible to S. aureus when neutrophils are depleted or neutrophil recruitment is blocked. Furthermore, the resistance is shown not to be dependent on T or B cells, indicating that neutrophils are essential (36,44). Since the KI mice had lower body weights than wild-type mice of similar age, the sizes of the inocula were normalized on the basis of body weight (1.82 ϫ 10 6 CFU/g of body weight).…”