title: Nitric oxide is neither necessary nor sufficient for resolution of Plasmodium chabaudi malaria in mice.
abstract: Malaria is a life-threatening re-emerging disease, yet it is still not clear how bloodstage malarial parasites are killed. Nitric oxide (NO), which has potent anti-microbial activity, may represent an important killing mechanism. The production of NO during descending Plasmodium chabaudi parasitemia, a period when parasites are killed by the immune response, supports this concept. However, NOS20/0 and NOS30/0 mice as well as mice treated with NO synthase 2 (NOS2) inhibitors do not develop exacerbated malaria, indicating that NO production is not necessary for the suppression of P. chabaudi parasitemia. It is possible due to the plasticity in the immune response during malaria that Ab-mediated immunity is enhanced in the absence of NO, thereby explaining the lack of exacerbated malaria in NOS-deficient mice even though NO may function in protection. However, NOS2- and B cell-deficient mice, which cannot use Ab-mediated immunity, suppress their parasitemia with a similar time course as B cell-deficient controls. C57BL/6 mice treated with Propionibacterium acnes to elicit high levels of macrophage-derived NO have a similar time course of P. chabaudi parasitemia as P. acnes-treated NOS20/0 mice, which do not produce NO; this indicates that NO is not sufficient for parasite killing. Collectively, these results indicate that NO is not necessary or sufficient to resolve P. chabaudi malaria.
authors.affiliation: Departments of Microbiology and Immunology and Molecular and Cellular Physiology, Inflammation and Immunology Research Group, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. hvande@lsumc.edu
authors.forename: H C
authors.initials: HC
authors.lastname: van der Heyde
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Sun
authors.forename: M B
authors.initials: MB
authors.lastname: Grisham
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D007274:Injections, Intraperitoneal; D008288:Malaria / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018512:Parasitemia / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D016788:Plasmodium chabaudi / Q000254:growth & development / Q000276:immunology*; D011425:Propionibacterium acnes / Q000276:immunology
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse