Pregnancy impairs the innate immune resistance to Salmonella typhimurium leading to rapid fatal infection

J Immunol. 2007 Nov 1;179(9):6088-96. doi: 10.4049/jimmunol.179.9.6088.

Abstract

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 x 1/SvJ) develop a chronic infection. We found that virulent ST infection during pregnancy, in normally resistant 129 x 1/SvJ mice, evoked approximately 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 approximately 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 >10(5) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo Loss / immunology*
  • Embryo Loss / microbiology
  • Female
  • Immunity, Innate / immunology*
  • Interleukin-12 / blood
  • Interleukin-6 / blood
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Kinetics
  • Male
  • Mice
  • Pregnancy
  • Salmonella Infections / immunology*
  • Salmonella Infections / microbiology
  • Salmonella typhimurium / immunology*
  • Salmonella typhimurium / pathogenicity*
  • Spleen / immunology
  • Time Factors

Substances

  • Interleukin-6
  • Interleukin-12