Nonspecific antiviral immunity by formalin-fixed Coxiella burnetii is enhanced in the absence of nitric oxide.
Mice treated with a single injection of formalin-fixed Coxiella burnetii showed a significant increase in resistance to vaccinia virus (VV) infection compared to untreated mice. C. burnetii stimulated dramatically high levels of nitric oxide (NO) in the serum of treated mice, suggesting that NO might play a role in resistance to virus infection. To test this hypothesis, the effect of C. burnetii treatment on VV replication was examined in NOS2-/- and wild-type mice. C. burnetii treatment inhibited VV replication in both the knockout and wild-type mice but the effect was significantly greater in the NOS2-/- mice. Experiments in IFNgamma receptor knockout mice indicated that the nonspecific antiviral immunity induced by C. burnetii was dependent on IFNgamma and not NO. In the absence of NO, indoleamine 2,3-dioxygenase (IDO) was increased in C. burnetii-treated mice and this may contribute to the accelerated virus clearance in NOS2-/- mice.
Rolph
Michael S
MS
Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia.
Mahalingam
Surendran
S
Cowden
William B
WB
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016997:Coxiella burnetii / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005557:Formaldehyde; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014611:Vaccination; D014615:Vaccinia / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D014616:Vaccinia virus / Q000502:physiology; D014779:Virus Replication / Q000276:immunology; D000096743:Interferon gamma Receptor
D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D005557:Formaldehyde; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017471:Receptors, Interferon; D014366:Tryptophan Oxygenase; D000096743:Interferon gamma Receptor