Typhoid fever and gastroenteritis caused by Salmonella enterica species are increasing globally. Pregnancy poses a high risk, but it is unclear how maternal immunity to infection is altered. In mice, susceptible strains die of S. enterica serovar typhimurium (ST) infection within 7 days whereas resistant mice (129×1/SvJ) develop a chronic infection. We found that virulent ST infection during pregnancy, in normally resistant 129×1/SvJ mice, evoked ∼100% fetal loss and surprisingly >60% host fatality, with a median survival of 6 days. Splenic bacterial load was 1000-fold higher in pregnant mice. This correlated to a diminished splenic recruitment/expansion of innate immune cells: dendritic cells, neutrophils, and NK cells. In particular, the splenic expansion and activation of NK cells postinfection seen in nonpregnant mice was lacking in pregnancy. Most notably, pregnant-infected mice had decreased production of serum IL-12 and increased IL-6 levels. Moreover, uteroplacental tissue of pregnant-infected mice exhibited an ∼40-fold increase in IL-6 mRNA expression relative to noninfected placenta, whereas IL-12p40 was not increased. In vivo blocking of IL-6 significantly reduced the splenic bacterial burden in pregnant mice yet failed to prevent fetal loss. Fetal demise correlated to the rapidity of infection; by 14 h, ST expanded to >105 in the placenta and had reached the fetus. Therefore, the preferential placental expansion of ST plausibly altered the inflammatory response toward IL-6 and away from IL-12, reducing the recruitment/activation of splenic innate immune cells. Thus, highly virulent pathogens may use placental invasion to alter systemic host resistance to infection.
Maternal hosts generate a normal Listeria-specific adaptive immunity in particular CD8+ T-cell memory response suggesting that systemic listeriosis during pregnancy may be an immunopathology associated with placental infection.
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