Salmonella enterica serovar Typhimurium-induced placental inflammation and not bacterial burden correlates with pathology and fatal maternal disease.
Food-borne infections caused by Salmonella enterica species are increasing globally, and pregnancy poses a high risk. Pregnant mice rapidly succumb to S. enterica serovar Typhimurium infection. To determine the mechanisms involved, we addressed the role of inflammation and bacterial burden in causing placental and systemic disease. In vitro, choriocarcinoma cells were a highly conducive niche for intracellular S. Typhimurium proliferation. While infection of mice with S. Typhimurium wild-type (WT) and mutant (Delta aroA and Delta invA) strains led to profound pathogen proliferation and massive burden within placental cells, only the virulent WT S. Typhimurium infection evoked total fetal loss and adverse host outcome. This correlated with substantial placental expression of granulocyte colony-stimulating factor (G-CSF), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) and increased serum inflammatory cytokines/chemokines, such as G-CSF, IL-6, CCL1, and KC, evoked by WT S. Typhimurium infection. In contrast, infection with high doses of S. Typhimurium Delta aroA, despite causing massive placental infection, resulted in reduced inflammatory cellular and cytokine response. While S. Typhimurium WT bacteria were dispersed in large numbers across all regions of the placenta, including the deeper labyrinth trophoblast, S. Typhimurium Delta aroA bacteria localized primarily to the decidua. This correlated with the widespread placental necrosis accompanied by neutrophil infiltration evoked by the S. Typhimurium WT bacteria. Thus, the ability of Salmonella to localize to deeper layers of the placenta and the nature of inflammation triggered by the pathogen, rather than bacterial burden, profoundly influenced placental integrity and host survival.
Chattopadhyay
Anindita
A
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Canada.
Robinson
Nirmal
N
Sandhu
Jagdeep K
JK
Finlay
B Brett
BB
Sad
Subash
S
Krishnan
Lakshmi
L
D000818:Animals; D002460:Cell Line; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000382:microbiology / Q000473:pathology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D012481:Salmonella Infections, Animal / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity; D016019:Survival Analysis
D016207:Cytokines