IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice

Abstract

Staphylococcus aureus is the most common cause of skin and soft tissue infections, and rapidly emerging antibiotic-resistant strains are creating a serious public health concern. If immune-based therapies are to be an alternative to antibiotics, greater understanding is needed of the protective immune response against S. aureus infection in the skin. Although neutrophil recruitment is required for immunity against S. aureus, a role for T cells has been suggested. Here, we used a mouse model of S. aureus cutaneous infection to investigate the contribution of T cells to host defense. We found that mice deficient in γδ but not αβ T cells had substantially larger skin lesions with higher bacterial counts and impaired neutrophil recruitment compared with WT mice. This neutrophil recruitment was dependent upon epidermal Vγ5 + γδ T cell production of IL-17, but not IL-21 and IL-22. Furthermore, IL-17 induction required IL-1, TLR2, and IL-23 and was critical for host defense, since IL-17R-deficient mice had a phenotype similar to that of γδ T cell-deficient mice. Importantly, γδ T cell-deficient mice inoculated with S. aureus and treated with a single dose of recombinant IL-17 had lesion sizes and bacterial counts resembling those of WT mice, demonstrating that IL-17 could restore the impaired immunity in these mice. Our study defines what we believe to be a novel role for IL-17-producing epidermal γδ T cells in innate immunity against S. aureus cutaneous infection.

IL-10 Plays Opposing Roles during Staphylococcus aureus Systemic and Localized Infections

“…3A). This is consistent with previous studies that have shown that IFN-gR 2/2 mice had lesion sizes and bacterial burdens similar to those of WT mice following an S. aureus skin infection (34). Overall, these results demonstrate that during acute S. aureus skin infection, IL-10 is capable of dampening down local proinflammatory responses and in particular gd + T cell responses, which facilitates persistence of the infection.…”

“…11). gd + T cells have previously been shown to be critically important for controlling bacterial burden within the skin during S. aureus s.c. infection where they direct neutrophil recruitment to the skin site (34). In line with this, we observed a significant increase in gd + T cells locally in the skin at 8 h postinfection in the absence of IL-10 (Fig.…”

Safety and immunogenicity of a recombinant Staphylococcus aureus α-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults

“…[37][38][39] We did not evaluate the a-toxin specific T-cell responses, which is a limitation of this study, and instead focused on evaluating the functionality of the anti-rAT antibodies generated by vaccination. Good seroresponse rates to the rAT vaccine were observed, with higher neutralizing antibody titers noted at the 50 mg rAT dose as compared to the 25 rAT mg dose in both monovalent and bivalent doses.…”

γδ-T cells: an unpolished sword in human anti-infection immunity

“…Both resident and circulating cd-T cells accumulate quickly around invasive pathogens and induce efficient anti-infection responses through collaboration with neighboring immune cells. 99 cd-T cells enhance the anti-infection capabilities of resident macrophages and NK cells, 100,101 promote the maturation of DCs 6,102 and improve the invasion resistance of epithelial cells. 103,104 Importantly, the dynamic interaction between cd-T cells and their neighbors induces cd-T cells in anti-infection immunity J Zheng et al 52 TCR selection of cd-T cells in situ, leading to more precise responses against specific pathogens.…”

“…4,5 The roles of cd-T cells are multifaceted and correlate with their distribution and differentiation. 2 On the one hand, epidermal cd-T cells play an indispensable role in limiting and eliminating invasive pathogens and recruiting inflammatory cells to infected locations, 6,7 while skin cd-T cells promote tissue repair by producing keratinocyte growth factor. 8 On the other hand, some cd-T cells, especially IL-17-producing cd-T cells, have been confirmed to be involved in the pathogenesis of transplantation rejection, 9 autoimmune diseases, [10][11][12][13] inflammatory diseases 14,15 and allergy 16 in human and animal models.…”