The role of toll-like receptors in the immune-adrenal crosstalk.
Sepsis and septic shock remain major health concerns worldwide, and rapid activation of adrenal steroid release is a key event in the organism's first line of defense during this form of severe illness. Toll-like receptors (TLRs) are critical in the early immune response upon bacterial infection, and recent data from our lab demonstrate a novel link between the innate immune system and the adrenal stress response mediated by TLRs. Glucocorticoids and TLRs regulate each other in a bidirectional way. Bacterial toxins acting through TLRs directly activate adrenocortical steroid release. TLR-2 and TLR-4 are expressed in human and mice adrenals and TLR-2 deficiency is associated with an impaired glucocorticoid response. Furthermore, TLR-2 deficiency in mice is associated with marked cellular alterations in adrenocortical tissue. TLR-2-deficient mice have an impaired adrenal corticosterone release following inflammatory stress induced by bacterial cell wall compounds. This defect appears to be associated with a decrease in systemic and intraadrenal cytokine expression. In conclusion, TLRs play a crucial role in the immune-adrenal crosstalk. This close functional relationship needs to be considered in the treatment of inflammatory diseases requiring an intact adrenal stress response.
Bornstein
S R
SR
Department of Anesthesiology, Heinrich Heine University, Düsseldorf, Germany. Stefan.Bornstein@uniklinikum-dresden.de
Ziegler
C G
CG
Krug
A W
AW
Kanczkowski
W
W
Rettori
V
V
McCann
S M
SM
Wirth
M
M
Zacharowski
K
K
D000302:Adrenal Cortex / Q000276:immunology*; D000818:Animals; D006801:Humans; D007107:Immune System / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000276:immunology; D020239:Receptor Cross-Talk / Q000276:immunology; D018805:Sepsis / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
D051193:Toll-Like Receptors