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Infection and Immunity, November 2000, p. 6101-6107, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

NO Contributes to Proliferative Suppression in a Murine Model of Filariasis

Richard A. O'Connor, Jessica S. Jenson, and Eileen Devaney*

Department of Veterinary Parasitology, University of Glasgow, Glasgow G61 1QH, United Kingdom

Received 26 June 2000/Returned for modification 1 August 2000/Accepted 7 August 2000

Infection of BALB/c mice with microfilariae (mf) of Brugia pahangi leads to the suppression of antigen (Ag)-specific proliferative responses in the spleen. The proliferative defect is dependent on inducible nitric oxide synthase (iNOS) activity, since inhibition of iNOS with either L-N-monomethyl arginine (L-NMMA) or aminoguanidine reversed defective proliferation. Splenocytes from mf-infected animals produce high levels of gamma interferon (IFN-gamma ) upon in vitro restimulation with Ag, and experiments in IFN-gamma receptor-deficient (IFN-gamma R-/-) mice demonstrated that signaling via the IFN-gamma R is essential in the induction of NO production and subsequent proliferative suppression. Restimulation of splenocytes from mf-infected animals with an extract of Acanthocheilonema viteae, a related filarial worm which lacks endosymbiotic bacteria, also resulted in NO production and proliferative suppression, demonstrating that lipopolysaccharide of bacterial origin is not essential to the induction of iNOS activity. These results extend previous observations that infection with different life cycle stages of Brugia leads to the development of differentially polarized immune responses and demonstrate one method by which these differences may exert their effects on the proliferative potential of cells from infected animals.


* Corresponding author. Mailing address: Department of Veterinary Parasitology, University of Glasgow, Bearsden Rd., Glasgow G61 1QH, United Kingdom. Phone: 44 (0) 141 330 5751. Fax: 44 (0) 141-330-5603. E-mail: e.devaney{at}vet.gla.ac.uk.


Infection and Immunity, November 2000, p. 6101-6107, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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