Inducible nitric oxide synthase is not essential for control of Trypanosoma cruzi infection in mice.
Immune control of many intracellular pathogens, including Trypanosoma cruzi, is reported to be dependent on the production of nitric oxide. In this study, we show that mice deficient in inducible nitric oxide synthase (iNOS or NOS2) exhibit resistance to T. cruzi infection that is comparable to that of wild-type mice. This is the case for two iNOS-deficient mouse strains, Nos2(tm1Lau) and Nos2 N5, infected with the Brazil or Tulahuen strain of T. cruzi. In all cases, blood parasitemia, tissue parasite load, and survival rates are similar between wild-type and iNOS-deficient mice. In contrast, both wild-type and Nos2(tm1Lau) mice died within 32 days postinfection when treated with the nitric oxide synthase inhibitor aminoguanidine. Increased transcription of NOS1 or NOS3 is not found in iNOS-knockout (KO) mice, indicating that the absence of nitric oxide production through iNOS is not compensated for by increased production of other NOS isoforms. However, Nos2(tm1Lau) mice exhibit enhanced expression of tumor necrosis factor alpha, interleukin-1, and macrophage inflammatory protein 1alpha compared to that of wild-type mice, and these alterations may in part compensate for the lack of iNOS. These results clearly show that iNOS is not required for control of T. cruzi infection in mice.
Cummings
Kara L
KL
Center for Tropical and Emerging Global Diseases, 623 Biological Sciences Building, University of Georgia, Athens, GA 30602, USA.
Tarleton
Rick L
RL
D000818:Animals; D014355:Chagas Disease / Q000201:enzymology*; D016207:Cytokines / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000201:enzymology*
D016207:Cytokines; D012333:RNA, Messenger; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse