We propose the following gaps in knowledge should be addressed: 1) how the SNS modulates our defence barriers during bacterial infections, 2) how endogenous SNS signals modulate the immune response during sepsis, 3) the immune cell-intrinsic functions of SNS signalling during sepsis through the generation of new inducible, conditional AR-deficient genetic animal models, and 4) the therapeutic efficacy of AR agonism/antagonism in clinically achievable therapeutic windows in preclinical models of sepsis with standard-care practices. The gene discussed is AR; the disease is Sepsis.