Immune changes during acute cold/restraint stress-induced inhibition of host resistance to Listeria.
Experiments were conducted to delineate the cellular changes modulated by acute cold/restraint stress (ACRS), a physical and psychological stressor, in response to a Listeria monocytogenes(LM) infection. In addition to wild type (WT) BALB/c mice, CD4-deficient (CD4-/-) BALB/c mice, which have no effective adaptive immunity, were used to determine the involvement of adaptive versus innate immunity. ACRS-induced suppression of host resistance to LM was not observed in CD4-/- mice, suggesting the involvement of CD4+T cells in the acute cold/restraint stress (ACRS)-induced inhibition. The in vivo splenic leukocyte phenotypes and activities of WT BALB/c mice after infection and in vitro lymphocyte responses to heat-killed LM (HKLM) also were examined. There were no significant differences in the numbers of splenic T and B lymphocytes, natural killer cells, macrophages, or neutrophils between nonstressed and ACRS-treated WT mice. However, higher levels of activated T cells and non-T lymphocytes were observed in the ACRS-treated mice; beta-adrenergic receptor (beta-ADR) antagonists (propranolol and atenolol) eliminated these elevated levels of activation, as well as the ACRS-induced suppression of host resistance. ACRS and control mice also had equivalent activation of macrophages. With in vitro HKLM stimulation, splenocytes from ACRS-treated mice produced significantly higher levels of IFNgamma and slightly higher levels of IL-6 in comparison with the nonstressed mice, although equivalent levels of lymphocyte proliferation were obtained. Additionally, ACRS-treated mice showed comparable elevation of serum nitric oxide after infection, indicating macrophage bactericidal activity similar to nonstressed mice. Thus, it appears that ACRS inhibits host resistance through regulatory CD4+ T cells and/or effector cell functions downstream of CD4+ T cell activation, as well as through beta-ADR signaling, in that blockage of these receptors appears to aid host defenses by means other than elevation of helper T cell activity. Because CD4 T cell deficiency and beta-ADR blockage produced equivalent effects, beta-ADR+ CD4+ T cells may have a negative role on host defenses after ACRS.
Cao
Ling
L
Laboratory of Clinical and Environmental Endocrinology and Immunology, Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
Hudson
Chad A
CA
Lawrence
David A
DA
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D020022:Genetic Predisposition to Disease; D007036:Hypothermia, Induced; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007121:Immunocompetence / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000523:psychology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D012149:Restraint, Physical; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013312:Stress, Physiological / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
D000319:Adrenergic beta-Antagonists; D015704:CD4 Antigens; D016207:Cytokines; D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide