Pregnancy impairs the innate immune resistance to Salmonella typhimurium leading to rapid fatal infection: J.Immunol.

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TypeArticle
Journal titleJ Immunol
Volume179
Issue9
Pages60886096; # of pages: 9
SubjectAnimals; bacterial; Blood; Canada; cell; CELLS; cytology; Embryo Loss; EXPRESSION; Female; Immunity,Natural; immunology; INFECTION; Interleukin-12; Interleukin-6; Killer Cells,Natural; Kinetics; Male; Mice; Microbiology; pathogenicity; Pregnancy; Salmonella; Salmonella Infections; Salmonella typhimurium; Serum; Spleen; STRAIN; STRAINS; Time Factors
AbstractTyphoid 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 date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberPEJCICKARAPETRO2007
NPARC number9378735
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Record identifiera7a4da73-a90e-4bd2-9681-c149ebc4e636
Record created2009-07-10
Record modified2016-05-09
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