期刊
JOURNAL OF IMMUNOLOGY
卷 178, 期 8, 页码 4876-4884出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.8.4876
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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 beta-adrenoceptors (beta ARs). We now show that impaired host resistance by CR cannot be accounted for by a decrease in LM-specific (listeriolysin O91-99 tetramer(+)) effector CD8(+) T cells; this result is consistent with previous observations that CR-induced effects are mainly limited to early anti-LM responses. beta 2-Adrenoceptor (beta 2AR)(-/-) FVB/NJ and wild-type FVB/NJ mice had equivalent anti-LM defenses, whereas beta 1-adrenoceptor (beta 1AR)(-/-) FVB/NJ mice had lower levels of LM even when subjected to CR treatment. Additionally, host-resistance competency of beta 1AR(-/-) mice could be transferred to irradiated wild-type mice reconstituted with, beta 1AR(-/-) bone marrow progenitors and spleen cells, indicating that beta 1AR signaling on immune cells reduces anti-LM responses. beta 1AR(-/-) mice had improved cellular (delayed-type hypersensitivity) responses while beta 2AR(-/-) mice had improved Immoral responses (IgG1, IgG2, and IgM), a result that further explains the strain differences in LM defenses. CR-induced expression of beta 1AR and beta 2AR mRNA was assessed by real-time PCR. CR treatment significantly increased beta 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, beta 1AR signaling has immunomodulatory effects on early cell-mediated immune responses; a lack of beta 1AR signaling improves antilisterial defenses and cell-mediated immunity, in general.
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