The Effect Of Nitric Oxide On Resistance To A Blood Flagellate In Carp     Jeroen Saeij, Willem B. Van Muiswinkel and Geert F. Wiegertjes   Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University, P.O. Box 338, 6700 AH Wageningen, The Netherlands     There is evidence for an antibody-mediated immune response against the kinetoplastid parasite, Trypanoplasma borreli, in their natural host the common carp (Cyprinus carpio). However, the mechanisms to persist in this immunocompetent host are not known. A common mechanism used by parasites to evade the host immune system is immunosuppression. A wide variety of parasites induce host macrophages to produce nitric oxide (NO), which could have an immunosuppressive effect.   To investigate the role of NO carp were infected with T. borreli and injected daily with an NO-inhibitor (amino-guanidine) or saline (control). Carp injected with NO-inhibitor showed increased survival, lower parasitaemia and lower nitrate levels in serum. This indicates that although in vitro NO seemed to be toxic for the parasite in vivo it has no effect on the parasite. On the contrary NO production seemed to be harmful to the carp. Additional experiments showed that the NO produced during infection with T. borreli leads to immunosuppression. Proliferation of head kidney (but not spleen or blood) lymphocytes after stimulation with ConA or LPS was inhibited in infected carp. Addition of NO-inhibitor restored proliferation.  In conclusion, we found evidence that the induction of NO by T. borreli helps this parasite to evade or suppress the immune system of carp.