TY  - JOUR
U1  - Wissenschaftlicher Artikel
A1  - Bonifacius, Agnes
A1  - Goldmann, Oliver
A1  - Floess, Stefan
A1  - Holtfreter, Silva
A1  - Robert, Philippe A.
A1  - Nordengrün, Maria
A1  - Kruse, Friederike
A1  - Lochner, Matthias
A1  - Falk, Christine S.
A1  - Schmitz, Ingo
A1  - Bröker, Barbara M.
A1  - Medina, Eva
A1  - Huehn, Jochen
T1  - Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses
JF  - Frontiers in Immunology
N2  - Staphylococcus aureus can cause life-threatening diseases, and hospital- as well as community-associated antibiotic-resistant strains are an emerging global public health problem. Therefore, prophylactic vaccines or immune-based therapies are considered as alternative treatment opportunities. To develop such novel treatment approaches, a better understanding of the bacterial virulence and immune evasion mechanisms and their potential effects on immune-based therapies is essential. One important staphylococcal virulence factor is alpha-toxin, which is able to disrupt the epithelial barrier in order to establish infection. In addition, alpha-toxin has been reported to modulate other cell types including immune cells. Since CD4+ T cell-mediated immunity is required for protection against S. aureus infection, we were interested in the ability of alpha-toxin to directly modulate CD4+ T cells. To address this, murine naïve CD4+ T cells were differentiated in vitro into effector T cell subsets in the presence of alpha-toxin. Interestingly, alpha-toxin induced death of Th1-polarized cells, while cells polarized under Th17 conditions showed a high resistance toward increasing concentrations of this toxin. These effects could neither be explained by differential expression of the cellular alpha-toxin receptor ADAM10 nor by differential activation of caspases, but might result from an increased susceptibility of Th1 cells toward Ca2+-mediated activation-induced cell death. In accordance with the in vitro findings, an alpha-toxin-dependent decrease of Th1 and concomitant increase of Th17 cells was observed in vivo during S. aureus bacteremia. Interestingly, corresponding subsets of innate lymphoid cells and γδ T cells were similarly affected, suggesting a more general effect of alpha-toxin on the modulation of type 1 and type 3 immune responses. In conclusion, we have identified a novel alpha-toxin-dependent immunomodulatory strategy of S. aureus, which can directly act on CD4+ T cells and might be exploited for the development of novel immune-based therapeutic approaches to treat infections with antibiotic-resistant S. aureus strains.
KW  - -
KW  - CD4
KW  - alpha-toxin
KW  - innate lymphoid cells
KW  - γδ T cells
Y1  - 2020
UN  - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-38973
SN  - 1664-3224
SS  - 1664-3224
U6  - https://doi.org/10.3389/fimmu.2020.01579
DO  - https://doi.org/10.3389/fimmu.2020.01579
VL  - 11
PB  - Frontiers Media S.A.
ER  -