The Journal of Immunology, Vol 156, Issue 2 644-652, Copyright © 1996 by American Association of Immunologists

ARTICLES

Pregnancy impairs resistance of C57BL/6 mice to Leishmania major infection and causes decreased antigen-specific IFN-gamma response and increased production of T helper 2 cytokines

L Krishnan, LJ Guilbert, AS Russell, TG Wegmann, TR Mosmann and M Belosevic
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.

Resolution of cutaneous leishmaniasis in infected mice is associated with a polarized Th1 immune response by the host, whereas maternal immune responses during pregnancy appear to be biased toward humoral (Th2) and away from cell-mediated (Th1) responses. The objective of this study was to evaluate whether the putative Th2 bias in pregnant C57BL/6 mice would impair their normal ability to mount a curative Th1 response against Leishmania major infection. Pregnant C57BL/6 mice developed larger cutaneous lesions that showed no signs of resolution up to 70 days after infection. The infection appeared to be contained but not cured, as the footpad lesion remained stable, neither decreasing (as in normal C57BL/6 mice) nor showing uncontrolled expansion leading to death (as in susceptible mouse strains such as BALB/c). The number of parasites harvested from the footpads of pregnant mice was markedly higher than controls throughout the course of infection. The increased severity of infection in pregnant mice was accompanied by reduced IFN-gamma and increased IL-4, IL-5, and IL-10 production by spleen and popliteal lymph node cells stimulated in vitro with Leishmania Ags. Furthermore, IgG1 was elevated in the serum of pregnant mice as opposed to an increase of IgG2a in infected but nonpregnant controls. These observations support the existence of a bias toward Th2 cytokine expression during pregnancy and suggest that these cytokines effectively down-regulate the course of a normal Th1 response against a parasite infection in the periphery.

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