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Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2018 Mar 01; Vol. 128 (3), pp. 1026-1042. Date of Electronic Publication: 2018 Feb 05. - Publication Year :
- 2018
-
Abstract
- The mechanisms that mediate durable protection against Staphylococcus aureus skin reinfections are unclear, as recurrences are common despite high antibody titers and memory T cells. Here, we developed a mouse model of S. aureus skin reinfection to investigate protective memory responses. In contrast with WT mice, IL-1β-deficient mice exhibited poor neutrophil recruitment and bacterial clearance during primary infection that was rescued during secondary S. aureus challenge. The γδ T cells from skin-draining LNs utilized compensatory T cell-intrinsic TLR2/MyD88 signaling to mediate rescue by trafficking and producing TNF and IFN-γ, which restored neutrophil recruitment and promoted bacterial clearance. RNA-sequencing (RNA-seq) of the LNs revealed a clonotypic S. aureus-induced γδ T cell expansion with a complementarity-determining region 3 (CDR3) aa sequence identical to that of invariant Vγ5+ dendritic epidermal T cells. However, this T cell receptor γ (TRG) aa sequence of the dominant CDR3 sequence was generated from multiple gene rearrangements of TRGV5 and TRGV6, indicating clonotypic expansion. TNF- and IFN-γ-producing γδ T cells were also expanded in peripheral blood of IRAK4-deficient humans no longer predisposed to S. aureus skin infections. Thus, clonally expanded γδ T cells represent a mechanism for long-lasting immunity against recurrent S. aureus skin infections.
- Subjects :
- Animals
Female
Gene Rearrangement
Interferon-gamma immunology
Interleukin-17 immunology
Interleukin-1beta immunology
Interleukins immunology
Male
Mice
Mice, Inbred C57BL
Neutrophil Infiltration
Neutrophils cytology
Receptors, Antigen, T-Cell, gamma-delta metabolism
Sequence Analysis, RNA
Signal Transduction
Staphylococcus aureus
Tumor Necrosis Factor-alpha immunology
Interleukin-22
Intraepithelial Lymphocytes immunology
Skin Diseases, Bacterial immunology
Staphylococcal Infections immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 128
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 29400698
- Full Text :
- https://doi.org/10.1172/JCI96481