TY - JOUR
T1 - Differential regulation of macrophage interleukin-1 (IL-1), IL-12, and CD80-CD86 by two bacterial toxins
AU - Foss, Dennis L.
AU - Zilliox, Michael J.
AU - Murtaugh, Michael P
PY - 1999
Y1 - 1999
N2 - The ability of innate immune cells to differentially respond to various bacterial components provides a mechanism by which the acquired immune response may be tailored to specific pathogens. The response of innate immune cells to bacterial components provides regulatory signals to cognate immune cells. These signals include secreted cytokines and costimulatory molecules, and to a large extent they determine the quantitative and qualitative nature of the immune response. In order to determine if innate immune cells can differentially respond to bacterial components, we compared the responses of macrophages to two bacterially derived molecules, cholera toxin (CT) and lipopolysaccharide (LPS). We found that CT and LPS differentially regulated the expression of interleukin-12 (IL-12) and CD80-CD86 but not that of IL- 1β. LPS and CT each induced IL-1β expression in macrophages, while only LPS induced IL-12 and only CT induced CD80-CD86. These differences were markedly potentiated in gamma interferon (IFN-γ)-treated macrophages, in which LPS potently induced IL-12 and CD80-CD86 expression. In contrast, IFN-γ treatment had no effect on the expression of IL-1β. These results define a molecular basis for the differential pathogenicities of bacterial toxins and are relevant to the design of vaccine adjuvants able to selectively induce desired types of immunity.
AB - The ability of innate immune cells to differentially respond to various bacterial components provides a mechanism by which the acquired immune response may be tailored to specific pathogens. The response of innate immune cells to bacterial components provides regulatory signals to cognate immune cells. These signals include secreted cytokines and costimulatory molecules, and to a large extent they determine the quantitative and qualitative nature of the immune response. In order to determine if innate immune cells can differentially respond to bacterial components, we compared the responses of macrophages to two bacterially derived molecules, cholera toxin (CT) and lipopolysaccharide (LPS). We found that CT and LPS differentially regulated the expression of interleukin-12 (IL-12) and CD80-CD86 but not that of IL- 1β. LPS and CT each induced IL-1β expression in macrophages, while only LPS induced IL-12 and only CT induced CD80-CD86. These differences were markedly potentiated in gamma interferon (IFN-γ)-treated macrophages, in which LPS potently induced IL-12 and CD80-CD86 expression. In contrast, IFN-γ treatment had no effect on the expression of IL-1β. These results define a molecular basis for the differential pathogenicities of bacterial toxins and are relevant to the design of vaccine adjuvants able to selectively induce desired types of immunity.
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U2 - 10.1128/iai.67.10.5275-5281.1999
DO - 10.1128/iai.67.10.5275-5281.1999
M3 - Article
C2 - 10496906
AN - SCOPUS:0344604529
SN - 0019-9567
VL - 67
SP - 5275
EP - 5281
JO - Infection and immunity
JF - Infection and immunity
IS - 10
ER -