T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resorptions. Correlation with increased IFN-gamma and TNF and reduced IL-10 production by placental cells.
Maternal immune responses can influence fetal survival and several cytokines have harmful or protective effects on pregnancy. The Th1 cytokines IFN-gamma and IL-2 can cause fetal loss, whereas the Th2 cytokine IL-10 is protective. However, infections such as leishmaniasis show the opposite pattern: resistance is associated with the preferential mounting of a Th1 response, whereas a Th2 response exacerbates the disease. We therefore asked whether the curative Th1 response against Leishmania major in genetically resistant C57BL/6 mice, would compromise concurrent pregnancy. The number of resorptions as assessed by uterine scars was significantly increased in infected C57BL/6 mice and this was associated with a decreased production by placental cells of the Th2 cytokines IL-4 and IL-10 and increased production of IFN-gamma and TNF. Interestingly, the frequency of pregnancy failure before implantation in C57BL/6 mice was also substantially increased. In contrast to C57BL/6 mice, early infection did not reduce implantations in BALB/c mice that mount a Th2 anti-L. major response and succumb to infection. For both resorptions and implantations, there appeared to be a short period early in infection that was detrimental to pregnancy, followed by a period with lesser effects, and a later period that again induced higher resorptions or pre-implantation losses. These results suggest that a beneficial anti-parasite Th1 response can adversely affect pregnancy outcome. Furthermore, Th1 cytokines may be deleterious for not only placental maintenance but also preimplantation events.
Krishnan
L
L
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
Guilbert
L J
LJ
Wegmann
T G
TG
Belosevic
M
M
Mosmann
T R
TR
D000818:Animals; D004198:Disease Susceptibility / Q000276:immunology; D010064:Embryo Implantation; D005260:Female; D005327:Fetal Resorption / Q000209:etiology*; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL / Q000276:immunology / Q000469:parasitology*; D010920:Placenta / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology*; D011256:Pregnancy Outcome; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma