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Mucosa-Associated Invariant T Cell Hypersensitivity to Staphylococcus aureus Leukocidin ED and Its Modulation by Activation.
Boulouis, Caroline; Leeansyah, Edwin; Mairpady Shambat, Srikanth; Norrby-Teglund, Anna; Sandberg, Johan K.
Afiliação
  • Boulouis C; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Leeansyah E; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Mairpady Shambat S; Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, People's Republic of China; and.
  • Norrby-Teglund A; Precision Medicine and Healthcare Research Center, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, People's Republic of China.
  • Sandberg JK; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
J Immunol ; 208(5): 1170-1179, 2022 03 01.
Article em En | MEDLINE | ID: mdl-35140134
Mucosa-associated invariant T (MAIT) cells recognize bacterial riboflavin metabolite Ags presented by MHC class Ib-related protein (MR1) and play important roles in immune control of microbes that synthesize riboflavin. This includes the pathobiont Staphylococcus aureus, which can also express a range of virulence factors, including the secreted toxin leukocidin ED (LukED). In this study, we found that human MAIT cells are hypersensitive to LukED-mediated lysis and lost on exposure to the toxin, leaving a T cell population devoid of MAIT cells. The cytolytic effect of LukED on MAIT cells was rapid and occurred at toxin concentrations lower than those required for toxicity against conventional T cells. Furthermore, this coincided with high MAIT cell expression of CCR5, and loss of these cells was efficiently inhibited by the CCR5 inhibitor maraviroc. Interestingly, exposure and preactivation of MAIT cells with IL-12 and IL-18, or activation via TCR triggering, partially protected from LukED toxicity. Furthermore, analysis of NK cells indicated that LukED targeted the mature cytotoxic CD57+ NK cell subset in a CCR5-independent manner. Overall, these results indicate that LukED efficiently eliminates immune cells that can respond rapidly to S. aureus in an innate fashion without the need for clonal expansion, and that MAIT cells are exceptionally vulnerable to this toxin. Thus, the findings support a model where LukED secretion may allow S. aureus to avoid recognition by the rapid cell-mediated responses mediated by MAIT cells and NK cells.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Staphylococcus aureus / Células Matadoras Naturais / Receptores CCR5 / Evasão da Resposta Imune / Células T Invariantes Associadas à Mucosa / Leucocidinas Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Staphylococcus aureus / Células Matadoras Naturais / Receptores CCR5 / Evasão da Resposta Imune / Células T Invariantes Associadas à Mucosa / Leucocidinas Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article