Inducible nitric-oxide synthase plays a minimal role in lymphocytic choriomeningitis virus-induced, T cell-mediated protective immunity and immunopathology
C. Bartholdy et al., Inducible nitric-oxide synthase plays a minimal role in lymphocytic choriomeningitis virus-induced, T cell-mediated protective immunity and immunopathology, J GEN VIROL, 80, 1999, pp. 2997-3005
By using mice with a targetted disruption in the gene encoding inducible ni
tric-oxide synthase (iNOS), we have studied the role of nitric oxide (NO) i
n lymphocytic choriomeningitis virus (LCMV)-induced, T cell-mediated protec
tive immunity and immunopathology. The afferent phase of the T cell-mediate
d immune response was found to be unaltered in iNOS-deficient mice compared
with wild-type C57BL/6 mice, and LCMV-induced general immunosuppression wa
s equally pronounced in both strains. In vivo analysis revealed identical k
inetics of virus clearance, as well as unaltered clinical severity of syste
mic LCMV infection in both strains. Concerning the outcome of intracerebral
infection, no significant differences were found between iNOS-deficient an
d wild-type mice in the number or composition of mononuclear cells found in
the cerebrospinal fluid on day 6 post-infection. Likewise, NO did not infl
uence the up-regulation of proinflammatory cytokine/chemokine genes signifi
cantly, nor did it influence the development of fatal meningitis. However,
a reduced virus-specific delayed-type hypersensitivity reaction was observe
d in iNOS-deficient mice compared with both IFN-gamma-deficient and wild-ty
pe mice. This might suggest a role of NO in regulating vascular reactivity
in the context of T cell-mediated inflammation. In conclusion, these findin
gs indicate a minimal role for iNOS/NO in the host response to LCMV. Except
for a reduced local oedema in the knockout mice, iNOS/NO seems to be redun
dant in controlling both the afferent and efferent phases of the T cell-med
iated immune response to LCMV infection.