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

John S. Cho, et al. The Journal of Clinical Investigation 120:1762-1772 (2010)

Speaker: Chih-Cheng Kang (康智程)                             Time: 13:10~14:00,Nov 03, 2010

Commentator: Dr. Huan-Yao Lei (黎煥耀 老師)           Place: Room 601

Abstract:

Staphylococcus aureus is a Gram-positive, extracellular bacterium that asymptomatically colonizes the human soft tissue and skin. It may cause a variety of diseases including pneumonia, meningitis, and sepsis. Recently, these infections have been increasingly caused by virulent antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA). If immune-based therapies are to be an alternative to antibiotics, greater understanding is needed of the protective immune response against S. aureus infection. Although neutrophil recruitment is required for immunity against S. aureus, a role for T cells is not clear. Therefore, the authors investigated the role of T cells in host to defense S. aureus infection in a cutanous infection mouse model. They demonstrated the mice deficient in γδ but not αβ T cells had markedly larger skin lesions, impaired bacterial clearance and decreased neutrophil recruitment compared with WT mice. Subsequently, the levels of IL-17, which trigger epithelial cells and fibroblasts to produce neutrophil recruitment factors and chemokines, were decreased in γδ T cell–deficient mice than WT mice after S. aureus cutaneous challenge.Furthermore, they demonstrated that TLR-mediated cytokines, including IL-1β and IL-23, were induced by S. aureus and mediated the production of IL-17. They observed IL-17 receptor–deficient mice had an impairment in host defense against S. aureus infection similar to those of γδ T cell–deficient mice. Furthermore, adminstration of IL-17A rescued the impaired phenotype induced by S. aureus in γδ T cell–deficient mice resmbling those of WT mice, while, adminstration of IL-17A mAb in WT mice increased the defective immunity against S. aureus infection. Thus, this study demonstrate that IL‑17–producing epidermal γδ T cells play a key role in innate immunity and provide a new immunomodulatory therapy against MRSA cutaneous infection

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