Title |
Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection
|
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Published in |
Journal of Clinical Investigation, February 2018
|
DOI | 10.1172/jci96481 |
Pubmed ID | |
Authors |
Carly A Dillen, Bret L Pinsker, Alina I Marusina, Alexander A Merleev, Orly N Farber, Haiyun Liu, Nathan K Archer, Da B Lee, Yu Wang, Roger V Ortines, Steven K Lee, Mark C Marchitto, Shuting S Cai, Alyssa G Ashbaugh, Larissa S May, Steven M Holland, Alexandra F Freeman, Loren G Miller, Michael R Yeaman, Scott I Simon, Joshua D Milner, Emanual Maverakis, Lloyd S Miller |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 24 | 63% |
Portugal | 1 | 3% |
Russia | 1 | 3% |
France | 1 | 3% |
Ireland | 1 | 3% |
United Kingdom | 1 | 3% |
Unknown | 9 | 24% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 31 | 82% |
Scientists | 6 | 16% |
Practitioners (doctors, other healthcare professionals) | 1 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 95 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 22 | 23% |
Researcher | 13 | 14% |
Student > Bachelor | 9 | 9% |
Student > Master | 7 | 7% |
Student > Doctoral Student | 6 | 6% |
Other | 13 | 14% |
Unknown | 25 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 29 | 31% |
Biochemistry, Genetics and Molecular Biology | 13 | 14% |
Agricultural and Biological Sciences | 10 | 11% |
Medicine and Dentistry | 9 | 9% |
Computer Science | 2 | 2% |
Other | 7 | 7% |
Unknown | 25 | 26% |