TY - JOUR
T1 - Macrophage Nitric Oxide Mediates Immunosuppression in Infectious Inflammation
AU - Eisenstein, Toby K.
AU - Huang, Duan
AU - Meissler, Joseph J.
AU - Al-Ramadi, Basel
N1 - Funding Information:
This work was supported by United States Public Health Service grant AI15613 from the National Institutes of Health. We thank BRUCE A. D. STOCKER for providing the strains of Salmonella.
PY - 1994
Y1 - 1994
N2 - A vaccine strain of live, attenuated Salmonella typhimurium induces profound immunosuppression in inoculated mice 7 days after injection. Immunosuppression to mitogens and inability to mount plaque-forming responses to sheep red blood cells occurs in spite of many parameters of upregulated macrophage function and protection against challenge with virulent Salmonella. Studies show that macrophage nitric oxide mediates the immunosuppression and presumably also the early-onset protective capacity of the vaccine. A model of ≪bystander lymphocyte autotoxicity≫ is presented to explain the mechanism of immunosuppression. The model proposes that Salmonella-activated macrophages generate nitric oxide which inactivates lymphocytes in the vicinity, so they become dysfunctional. Inhibition of nitric oxide by NG-monomethyl-Larginine reverses immunosuppression. Evidence is presented that supports a relationship between the microbial burden in the spleen, the degree of nitric oxide produced, and the extent of immunosuppression. It is proposed that this model of microbial immunosuppression mediated by nitric oxide is generalizable for understanding immunosuppression and loss of delayed-type hypersensitivity induced by other microbes, such as Mycobacteria and measles virus. The model could account for anergy during mycobacterial infections, particularly when the burden of acid-fast bacilli is high, as well as loss of skin test reactivity to tuberculin during measles infection.
AB - A vaccine strain of live, attenuated Salmonella typhimurium induces profound immunosuppression in inoculated mice 7 days after injection. Immunosuppression to mitogens and inability to mount plaque-forming responses to sheep red blood cells occurs in spite of many parameters of upregulated macrophage function and protection against challenge with virulent Salmonella. Studies show that macrophage nitric oxide mediates the immunosuppression and presumably also the early-onset protective capacity of the vaccine. A model of ≪bystander lymphocyte autotoxicity≫ is presented to explain the mechanism of immunosuppression. The model proposes that Salmonella-activated macrophages generate nitric oxide which inactivates lymphocytes in the vicinity, so they become dysfunctional. Inhibition of nitric oxide by NG-monomethyl-Larginine reverses immunosuppression. Evidence is presented that supports a relationship between the microbial burden in the spleen, the degree of nitric oxide produced, and the extent of immunosuppression. It is proposed that this model of microbial immunosuppression mediated by nitric oxide is generalizable for understanding immunosuppression and loss of delayed-type hypersensitivity induced by other microbes, such as Mycobacteria and measles virus. The model could account for anergy during mycobacterial infections, particularly when the burden of acid-fast bacilli is high, as well as loss of skin test reactivity to tuberculin during measles infection.
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U2 - 10.1016/S0171-2985(11)80455-9
DO - 10.1016/S0171-2985(11)80455-9
M3 - Article
C2 - 7713563
AN - SCOPUS:0028077005
SN - 0171-2985
VL - 191
SP - 493
EP - 502
JO - Zeitschrift für Immunitätsforschung und experimentelle Therapie
JF - Zeitschrift für Immunitätsforschung und experimentelle Therapie
IS - 4-5
ER -