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1-Adrenergic Receptors on Immune Cells Impair Innate Defenses against Listeria

Laboratory of Clinical and Experimental Endocrinology and Immunology, Wadsworth Center, New York State Department of Health, Albany, NY 12201

Cold restraint (CR) for 1 h elicits a psychological and physiological stress that inhibits host defenses against Listeria monocytogenes (LM). Previous analyses indicated that this inhibition is not due to depletion of B or T cells but is instead dependent on signaling through -adrenoceptors (ARs). We now show that impaired host resistance by CR cannot be accounted for by a decrease in LM-specific (listeriolysin O_91–99 tetramer⁺) effector CD8⁺ T cells; this result is consistent with previous observations that CR-induced effects are mainly limited to early anti-LM responses. 2-Adrenoceptor (2AR)^–/– FVB/NJ and wild-type FVB/NJ mice had equivalent anti-LM defenses, whereas 1-adrenoceptor (1AR)^–/– FVB/NJ mice had lower levels of LM even when subjected to CR treatment. Additionally, host-resistance competency of 1AR^–/– mice could be transferred to irradiated wild-type mice reconstituted with 1AR^–/– bone marrow progenitors and spleen cells, indicating that 1AR signaling on immune cells reduces anti-LM responses. 1AR^–/– mice had improved cellular (delayed-type hypersensitivity) responses while 2AR^–/– mice had improved humoral responses (IgG1, IgG2, and IgM), a result that further explains the strain differences in LM defenses. CR-induced expression of 1AR and 2AR mRNA was assessed by real-time PCR. CR treatment significantly increased AR mRNAs in Ficoll-purified and F4/80⁺-enhanced liver but not splenic homogenates, demonstrating an organ-specific effect of stress that alters host defenses. Finally, CR treatment induced early increases in perforin expression that may enhance immune cell apoptosis and interfere with LM clearance. In conclusion, 1AR signaling has immunomodulatory effects on early cell-mediated immune responses; a lack of 1AR signaling improves antilisterial defenses and cell-mediated immunity, in general.

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¹ Address correspondence and reprint requests to Dr. David A. Lawrence, Wadsworth Center, New York State Department of Health, Molecular Medicine, Empire State Plaza, C419, Albany, NY 12201. E-mail address: David.Lawrence{at}Wadsworth.org

² Abbreviations used in this paper: LM, Listeria monocytogenes; 1AR, 1-adrenoceptor; 2AR, 2-adrenoceptor; AR, -adrenoceptor; CORT, corticosterone; CR, cold restraint; DA, dopamine; DTH, delayed-type hypersensitivity; Epi, epinephrine; LLO_91–99, listeriolysin O_91–99; NE, norepinephrine; RT, room temperature; WT, wild type.