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Infection and Immunity, November 2000, p. 6101-6107, Vol. 68, No. 11
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-
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
) upon in vitro restimulation with Ag, and
experiments in IFN-
receptor-deficient (IFN-
R
/
)
mice demonstrated that signaling via the IFN-
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.
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