Nlrp-3-Driven Interleukin 17 Production by γδT Cells Controls Infection Outcomes during Staphylococcus aureus Surgical Site Infection
Open Access
- 1 December 2013
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 81 (12), 4478-4489
- https://doi.org/10.1128/iai.01026-13
Abstract
Recent work has identified T cells and the cytokines they produce as important correlates of immune protection during Staphylococcus aureus infections through the ability of these T cells to regulate local neutrophil responses. However, the specific T-cell subsets that are involved in coordinating protection at distinct sites of infection remains to be established. In this study, we identify for the first time an important role for γδT cells in controlling S. aureus surgical site infection (SSI). γδT cells are recruited to the wound site following S. aureus challenge, where they represent the primary source of interleukin 17 (IL-17), with a small contribution from other non-γδT cells. The IL-17 response is entirely dependent upon IL-1 receptor signaling. Using IL-17 receptor-deficient mice, we demonstrate that IL-17 is required to control bacterial clearance during S. aureus SSI. However, we demonstrate a strain-dependent requirement for γδT cells in this process due to the differential abilities of individual strains to activate IL-1β production. IL-1β processing relies upon activation of the Nlrp3 inflammasome complex, and we demonstrate that Nlrp3-deficient and IL-1 receptor-deficient mice have an impaired ability to control S. aureus SSI due to reduced production of IL-17 by γδT cells at the site of infection. Given that IL-17 has been identified as an important correlate of immune protection during S. aureus infection, it is vital that the unique cellular sources of this cytokine and mechanisms inducing its activation are identified at distinct sites of infection. Our study demonstrates that while IL-17 may be critically important for mediating immune protection during S. aureus SSI, the relative contribution of γδT cells to these protective effects may be strain dependent.Keywords
This publication has 48 references indexed in Scilit:
- A Systematic Analysis of the Peripheral and CNS Effects of Systemic LPS, IL-1Β, TNF-α and IL-6 Challenges in C57BL/6 MicePLOS ONE, 2013
- Toll-Like Receptor 4-Mediated Innate IL-10 Activates Antigen-Specific Regulatory T Cells and Confers Resistance to Bordetella pertussis by Inhibiting Inflammatory PathologyPublished by The American Association of Immunologists ,2003
- Role of gamma/delta T cell receptor-expressing lymphocytes in cutaneous infection caused byStaphylococcus aureusClinical and Experimental Immunology, 2003
- Endogenous Antimicrobial Peptides and Skin Infections in Atopic DermatitisNew England Journal of Medicine, 2002
- σBModulates Virulence Determinant Expression and Stress Resistance: Characterization of a FunctionalrsbUStrain Derived fromStaphylococcus aureus8325-4Journal of Bacteriology, 2002
- Interleukin-17 and Lung Host Defense againstKlebsiella pneumoniae InfectionAmerican Journal of Respiratory Cell and Molecular Biology, 2001
- Survival of Staphylococcus aureus Inside Neutrophils Contributes to InfectionPublished by The American Association of Immunologists ,2000
- Genetic analysis of thecap5locus ofStaphylococcus aureusFEMS Microbiology Letters, 1999
- Staphylococcus aureusInfectionsNew England Journal of Medicine, 1998
- T cell receptor δ gene mutant mice: Independent generation of αβ T cells and programmed rearrangements of γδ TCR genesCell, 1993