Acute cold/restraint stress inhibits host resistance to Listeria monocytogenes via beta1-adrenergic receptors.

We previously reported that acute cold/restraint stress (ACRS) significantly inhibits host resistance to Listeria monocytogenes (LM) in BALB/c mice and that the sympathetic nervous system plays a major role in this inhibition. Here, we have further investigated the involvement of adrenergic receptor (ADR) subtypes. beta-ADR antagonist propranolol, but not alpha-ADR antagonist phentolamine significantly enhanced host resistance of ACRS mice. Pro-inflammatory cytokine (IL-6, IL-1beta, and TNFalpha) and IFNgamma levels positively correlated with the LM levels in all groups of mice. Furthermore, beta1-ADR antagonist atenolol but not beta2-ADR antagonist ICI118,551 significantly decreased LM burden in ACRS mice. In addition, SCID mice on the same genetic background (BALB/c), which have no adaptive immune potential, were used to assess the immune responses targeted by ACRS. ACRS-induced suppression of host resistance was not observed in SCID mice, and propranolol pretreatment provided no further improvement of host resistance, indicating that ACRS mainly affects adaptive immunity, which is less critical in mice with greater innate than adaptive immunity. In summary, the data suggest that ACRS inhibition of host resistance to LM is mediated through beta1-ADR stimulation, which appears to directly or indirectly modify activation of T cells or subsequent T cell functions involved in adaptive immunity, thus inhibiting overall host resistance. Interestingly, with heightened innate immunity and the absence of adaptive immunity, as observed in the SCID mice, ACRS does not affect host resistance, which emphasizes the importance of innate immunity in defense against bacterial infection.