Toll-like receptor 4 plays a crucial role in the immune–adrenal response to systemic inflammatory response syndrome

Sepsis and septic shock are leading killers in the noncoronary intensive care unit, and they remain worldwide health concerns. The initial host defense against bacterial infections involves Toll-like receptors (TLRs), which detect and respond to microbial ligands. In addition, a coordinated response of the adrenal and immune systems is crucial for survival during severe inflammation. Previously, we demonstrated a link between the innate immune system and the endocrine stress response involving TLR-2. Like TLR-2, TLR-4 is also expressed in human and mouse adrenals. In the present work, by using a low dose of LPS to mimic systemic inflammatory response syndrome, we have revealed marked cellular alterations in adrenocortical tissue and an impaired adrenal corticosterone response in TLR-4−/− mice. Our findings demonstrate that TLR-4 is a key mediator in the crosstalks between the innate immune system and the endocrine stress response. Furthermore, TLR polymorphisms could contribute to the underlying mechanisms of impaired adrenal stress response in patients with bacterial sepsis. Fil: Zacharowski, Kai. Heinrich Heine University; Alemania. University of Dresden; Alemania Fil: Zacharowski, Paula A.. Heinrich Heine University; Alemania Fil: Koch, Alexander. Heinrich Heine University; Alemania Fil: Baban, Aida. Heinrich Heine University; Alemania Fil: Tran, Nguyen. Heinrich Heine University; Alemania Fil: Berkels, Reinhard. Heinrich Heine University; Alemania Fil: Papewalis, Claudia. Heinrich Heine University; Alemania Fil: Schulze Osthoff, Klaus. Heinrich Heine University; Alemania Fil: Knuefermann, Pascal. Universitaet Bonn; Alemania Fil: Zähringer, Ulrich. Research Center Borstel; Alemania Fil: Schumann, Ralf R.. Humboldt University; Alemania Fil: Besuhli, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: McCann, Samuel M.. Fil: Bornstein, Stefan R.. University of Dresden; Alemania