First Author | Dillen CA | Year | 2018 |
Journal | J Clin Invest | Volume | 128 |
Issue | 3 | Pages | 1026-1042 |
PubMed ID | 29400698 | Mgi Jnum | J:332511 |
Mgi Id | MGI:6150411 | Doi | 10.1172/JCI96481 |
Citation | Dillen CA, et al. (2018) Clonally expanded gammadelta T cells protect against Staphylococcus aureus skin reinfection. J Clin Invest 128(3):1026-1042 |
abstractText | 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-1beta-deficient mice exhibited poor neutrophil recruitment and bacterial clearance during primary infection that was rescued during secondary S. aureus challenge. The gammadelta T cells from skin-draining LNs utilized compensatory T cell-intrinsic TLR2/MyD88 signaling to mediate rescue by trafficking and producing TNF and IFN-gamma, which restored neutrophil recruitment and promoted bacterial clearance. RNA-sequencing (RNA-seq) of the LNs revealed a clonotypic S. aureus-induced gammadelta T cell expansion with a complementarity-determining region 3 (CDR3) aa sequence identical to that of invariant Vgamma5+ dendritic epidermal T cells. However, this T cell receptor gamma (TRG) aa sequence of the dominant CDR3 sequence was generated from multiple gene rearrangements of TRGV5 and TRGV6, indicating clonotypic expansion. TNF- and IFN-gamma-producing gammadelta T cells were also expanded in peripheral blood of IRAK4-deficient humans no longer predisposed to S. aureus skin infections. Thus, clonally expanded gammadelta T cells represent a mechanism for long-lasting immunity against recurrent S. aureus skin infections. |