Salmonella Enterica serovar Typhimurium Infection in Mouse Pregnancy
Loading...
Authors
Mohammad, Shuhiba
Date
Type
thesis
Language
eng
Keyword
Placenta , Foodborne Pathogens , Infection , Pregnancy
Alternative Title
Abstract
Salmonella are Gram-negative, intracellular food-borne pathogens that cause pregnancy
complications. In pregnant mice, Salmonella enterica serovar Typhimurium (S.Tm) infection results in
placental bacterial replication, inflammation, necrosis, and fetal loss by unknown mechanisms.
Necroptosis, or programmed necrosis mediated by RIPK3 (receptor-interacting protein kinase 3), an
inflammatory cell death pathway, is implicated in the pathogenesis of S.Tm in non-pregnant mice. This
goal of this thesis was to investigate the role of necroptosis in the pathogenesis of S.Tm infection during
mouse pregnancy. I hypothesized that elimination of the key necroptotic cell death protein RIPK3 would
decrease placental inflammation and trophoblast cell death, and increase conceptus survival compared to
controls.
Mice expressing a functional Slc11a1 (encodes the natural resistance-associated macrophage
protein 1, NRAMP1) gene with or without RIPK3 function (Ripk3-/-Slc11a1+/+ compared to Slc11a1+/+)
were infected with 103 S.Tm by tail vein injection on gestational day (GD) 12. Mice were euthanized on
GD 14 (48h post-infection) or GD 15 (72h post-infection) and implantation sites (IS) and maternal serum
were harvested for analyses.
In nearly all challenged mice (except one outlier), S.Tm were detected in most IS within a litter
but there was limited immune cell infiltration, placental damage or cell death in Slc11a1 competent mice
regardless of Ripk3 gene deletion. Maternal serum cytokine analyses confirmed lack of maternal immune
responses to S.Tm infection. IS amongst the litter of a single dam (Ripk3-/-Slc11a1+/+ at 72h postinfection)
displayed heavy but not universal placental S.Tm infection of decidual tissues and
spongiotrophoblast, associated with elevated maternal serum pro-inflammatory cytokines. S.Tm infection
of the fetal yolk sac (YS) was observed in 54.5% of IS from this dam. YS infection was confirmed in
archival samples in mice expressing Ripk3 with intact Slc11a1 and in mice lacking functional Slc11a1. In
Slc11a1 incompetent mice, S.Tm were detected in placental labyrinthine trophoblast. Based on the
available data, this thesis suggests that Ripk3 and necroptosis have no significant roles in either promotion
or prevention of progressive Salmonella infection during mouse pregnancy. It also provides pilot data that
NRAMP1 controls placental localization and lethality due to YS infection.
Description
Citation
Publisher
License
CC0 1.0 Universal
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.