PREGNANCY IMPAIRS RESISTANCE OF C57BL 6 MICE TO LEISHMANIA-MAJOR INFECTION AND CAUSES DECREASED ANTIGEN-SPECIFIC IFN-GAMMA RESPONSES AND INCREASED PRODUCTION OF T-HELPER-2 CYTOKINES/

Resolution of cutaneous leishmaniasis in infected mice is associated w ith a polarized Th1 immune response by the host, whereas maternal immu ne responses during pregnancy appear to be biased toward humoral (Th2) and away from cell-mediated (Th1) responses, The objective of this st udy was to evaluate whether the putative Th2 bias in pregnant C57BL/6 mice would impair their normal ability to mount a curative Th1 respons e against Leishmania major infection, Pregnant C57BL/6 mice developed larger cutaneous lesions that showed no signs of resolution up to 70 d ays after infection, The infection appeared to be contained but not cu red, as the footpad lesion remained stable, neither decreasing (as in normal C57BL/6 mice) nor showing uncontrolled expansion leading to dea th (as in susceptible mouse strains such as BALB/c), The number of par asites harvested from the footpads of pregnant mice was markedly highe r than controls throughout the course of infection, The increased seve rity of infection in pregnant mice was accompanied by reduced IFN-gamm a and increased IL-4, IL-5, and IL-10 production by spleen and poplite al lymph node cells stimulated in vitro with Leishmania Ags, Furthermo re, IgG1 was elevated in the serum of pregnant mice as opposed to an i ncrease of IgC2a in infected but nonpregnant controls, These observati ons support the existence of a bias toward Th2 cytokine expression dur ing pregnancy and suggest that these cytokines effectively down-regula te the course of a normal Th1 response against a parasite infection in the periphery.