TY - JOUR
T1 - Nitric oxide-mediated suppression of T cell responses during Trypanosoma brucei infection
T2 - Soluble trypanosome products and interferon-γ are synergistic inducers of nitric oxide synthase
AU - Sternberg, Jeremy M.
AU - Mabbott, Neil A.
PY - 1996/3/1
Y1 - 1996/3/1
N2 - African trypanosome infections result in lymphocyte unresponsiveness and anemia in the mammalian host. In murine infections, these effects are mediated by suppressor macrophages releasing nitric oxide (NO). We investigated the mechanism of activation of macrophages to produce NO during trypanosomiasis in vitro. A soluble component of trypanosome lysates induced NO synthesis in peritoneal macrophage cultures only when the macrophages were co-stimulated with interferon-gamma (IFN-γ). The macrophage-activating factor was also released in a soluble form by live bloodstream-form trypanosomes, but not procyclic trypanosomes. When splenocyte cultures were exposed to IFN-γ, and trypanosomes, an NO-dependent suppression of T cell proliferation occurred. This is similar to the suppression observed in the spleens of trypanosome-infected mice, suggesting that a combination of trypanosome-released macrophage-activating factors and IFN-γ are a trigger of immune dysfunction in trypanosomiasis.
AB - African trypanosome infections result in lymphocyte unresponsiveness and anemia in the mammalian host. In murine infections, these effects are mediated by suppressor macrophages releasing nitric oxide (NO). We investigated the mechanism of activation of macrophages to produce NO during trypanosomiasis in vitro. A soluble component of trypanosome lysates induced NO synthesis in peritoneal macrophage cultures only when the macrophages were co-stimulated with interferon-gamma (IFN-γ). The macrophage-activating factor was also released in a soluble form by live bloodstream-form trypanosomes, but not procyclic trypanosomes. When splenocyte cultures were exposed to IFN-γ, and trypanosomes, an NO-dependent suppression of T cell proliferation occurred. This is similar to the suppression observed in the spleens of trypanosome-infected mice, suggesting that a combination of trypanosome-released macrophage-activating factors and IFN-γ are a trigger of immune dysfunction in trypanosomiasis.
KW - Interferon-α
KW - Nitric oxide
KW - Trypanosoma brucei
UR - http://www.scopus.com/inward/record.url?scp=0029925710&partnerID=8YFLogxK
U2 - 10.1002/eji.1830260306
DO - 10.1002/eji.1830260306
M3 - Article
C2 - 8605918
AN - SCOPUS:0029925710
SN - 0014-2980
VL - 26
SP - 539
EP - 543
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 3
ER -