Th17 cell plasticity towards a T-bet-dependent Th1 phenotype is required for bacterial control in Staphylococcus aureus infection
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Th17 cell plasticity towards a T-bet-dependent Th1 phenotype is required for bacterial control in Staphylococcus aureus infection. / Bartsch, Patricia; Kilian, Christoph; Hellmig, Malte; Paust, Hans-Joachim; Borchers, Alina; Sivayoganathan, Amirrtavarshni; Enk, Leon; Zhao, Yu; Shaikh, Nikhat; Büttner, Henning; Wong, Milagros N; Puelles, Victor G; Wiech, Thorsten; Flavell, Richard; Huber, Tobias B; Turner, Jan-Eric; Bonn, Stefan; Huber, Samuel; Gagliani, Nicola; Mittrücker, Hans-Willi; Rohde, Holger; Panzer, Ulf; Krebs, Christian F.
in: PLOS PATHOG, Jahrgang 18, Nr. 4, 04.2022, S. e1010430.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Th17 cell plasticity towards a T-bet-dependent Th1 phenotype is required for bacterial control in Staphylococcus aureus infection
AU - Bartsch, Patricia
AU - Kilian, Christoph
AU - Hellmig, Malte
AU - Paust, Hans-Joachim
AU - Borchers, Alina
AU - Sivayoganathan, Amirrtavarshni
AU - Enk, Leon
AU - Zhao, Yu
AU - Shaikh, Nikhat
AU - Büttner, Henning
AU - Wong, Milagros N
AU - Puelles, Victor G
AU - Wiech, Thorsten
AU - Flavell, Richard
AU - Huber, Tobias B
AU - Turner, Jan-Eric
AU - Bonn, Stefan
AU - Huber, Samuel
AU - Gagliani, Nicola
AU - Mittrücker, Hans-Willi
AU - Rohde, Holger
AU - Panzer, Ulf
AU - Krebs, Christian F
PY - 2022/4
Y1 - 2022/4
N2 - Staphylococcus aureus is frequently detected in patients with sepsis and thus represents a major health burden worldwide. CD4+ T helper cells are involved in the immune response to S. aureus by supporting antibody production and phagocytosis. In particular, Th1 and Th17 cells secreting IFN-γ and IL-17A, are involved in the control of systemic S. aureus infections in humans and mice. To investigate the role of T cells in severe S. aureus infections, we established a mouse sepsis model in which the kidney was identified to be the organ with the highest bacterial load and abundance of Th17 cells. In this model, IL-17A but not IFN-γ was required for bacterial control. Using Il17aCre × R26YFP mice we could show that Th17 fate cells produce Th17 and Th1 cytokines, indicating a high degree of Th17 cell plasticity. Single cell RNA-sequencing of renal Th17 fate cells uncovered their heterogeneity and identified a cluster with a Th1 expression profile within the Th17 cell population, which was absent in mice with T-bet/Tbx21-deficiency in Th17 cells (Il17aCre x R26eYFP x Tbx21-flox). Blocking Th17 to Th1 transdifferentiation in Th17 fate cells in these mice resulted in increased S. aureus tissue loads. In summary, we highlight the impact of Th17 cells in controlling systemic S. aureus infections and show that T-bet expression by Th17 cells is required for bacterial clearance. While targeting the Th17 cell immune response is an important therapeutic option in autoimmunity, silencing Th17 cells might have detrimental effects in bacterial infections.
AB - Staphylococcus aureus is frequently detected in patients with sepsis and thus represents a major health burden worldwide. CD4+ T helper cells are involved in the immune response to S. aureus by supporting antibody production and phagocytosis. In particular, Th1 and Th17 cells secreting IFN-γ and IL-17A, are involved in the control of systemic S. aureus infections in humans and mice. To investigate the role of T cells in severe S. aureus infections, we established a mouse sepsis model in which the kidney was identified to be the organ with the highest bacterial load and abundance of Th17 cells. In this model, IL-17A but not IFN-γ was required for bacterial control. Using Il17aCre × R26YFP mice we could show that Th17 fate cells produce Th17 and Th1 cytokines, indicating a high degree of Th17 cell plasticity. Single cell RNA-sequencing of renal Th17 fate cells uncovered their heterogeneity and identified a cluster with a Th1 expression profile within the Th17 cell population, which was absent in mice with T-bet/Tbx21-deficiency in Th17 cells (Il17aCre x R26eYFP x Tbx21-flox). Blocking Th17 to Th1 transdifferentiation in Th17 fate cells in these mice resulted in increased S. aureus tissue loads. In summary, we highlight the impact of Th17 cells in controlling systemic S. aureus infections and show that T-bet expression by Th17 cells is required for bacterial clearance. While targeting the Th17 cell immune response is an important therapeutic option in autoimmunity, silencing Th17 cells might have detrimental effects in bacterial infections.
U2 - 10.1371/journal.ppat.1010430
DO - 10.1371/journal.ppat.1010430
M3 - SCORING: Journal article
C2 - 35446923
VL - 18
SP - e1010430
JO - PLOS PATHOG
JF - PLOS PATHOG
SN - 1553-7366
IS - 4
ER -
