PMID- 37795301
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231028
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 14
DP  - 2023
TI  - Syphilis and the host: multi-omic analysis of host cellular responses to 
      Treponema pallidum provides novel insight into syphilis pathogenesis.
PG  - 1254342
LID - 10.3389/fmicb.2023.1254342 [doi]
LID - 1254342
AB  - INTRODUCTION: Syphilis is a chronic, multi-stage infection caused by the 
      extracellular bacterium Treponema pallidum ssp. pallidum. Treponema pallidum 
      widely disseminates through the vasculature, crosses endothelial, blood-brain and 
      placental barriers, and establishes systemic infection. Although the capacity of 
      T. pallidum to traverse the endothelium is well-described, the response of 
      endothelial cells to T. pallidum exposure, and the contribution of this response 
      to treponemal traversal, is poorly understood. METHODS: To address this knowledge 
      gap, we used quantitative proteomics and cytokine profiling to characterize 
      endothelial responses to T. pallidum. RESULTS: Proteomic analyses detected 
      altered host pathways controlling extracellular matrix organization, necroptosis 
      and cell death, and innate immune signaling. Cytokine analyses of endothelial 
      cells exposed to T. pallidum revealed increased secretion of interleukin (IL)-6, 
      IL-8, and vascular endothelial growth factor (VEGF), and decreased secretion of 
      monocyte chemoattractant protein-1 (MCP-1). DISCUSSION: This study provides 
      insight into the molecular basis of syphilis disease symptoms and the enhanced 
      susceptibility of individuals infected with syphilis to HIV co-infection. These 
      investigations also enhance understanding of the host response to T. pallidum 
      exposure and the pathogenic strategies used by T. pallidum to disseminate and 
      persist within the host. Furthermore, our findings highlight the critical need 
      for inclusion of appropriate controls when conducting T. pallidum-host cell 
      interactions using in vitro- and in vivo-grown T. pallidum.
CI  - Copyright (c) 2023 Waugh, Ranasinghe, Gomez, Houston, Lithgow, Eshghi, Fleetwood, 
      Conway, Reynolds and Cameron.
FAU - Waugh, Sean
AU  - Waugh S
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Ranasinghe, Akash
AU  - Ranasinghe A
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Gomez, Alloysius
AU  - Gomez A
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Houston, Simon
AU  - Houston S
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Lithgow, Karen V
AU  - Lithgow KV
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Eshghi, Azad
AU  - Eshghi A
AD  - University of Victoria-Genome BC Proteomics Centre, Victoria, BC, Canada.
FAU - Fleetwood, Jenna
AU  - Fleetwood J
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Conway, Kate M E
AU  - Conway KME
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Reynolds, Lisa A
AU  - Reynolds LA
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Cameron, Caroline E
AU  - Cameron CE
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
AD  - Division of Allergy and Infectious Diseases, Department of Medicine, University 
      of Washington, Seattle, WA, United States.
LA  - eng
GR  - R37 AI051334/AI/NIAID NIH HHS/United States
GR  - U19 AI144133/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20230919
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
PMC - PMC10546344
OTO - NOTNLM
OT  - Treponema pallidum
OT  - disease symptoms
OT  - dissemination
OT  - proteomics
OT  - syphilis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/10/05 06:43
MHDA- 2023/10/05 06:44
PMCR- 2023/09/19
CRDT- 2023/10/05 04:09
PHST- 2023/07/07 00:00 [received]
PHST- 2023/09/01 00:00 [accepted]
PHST- 2023/10/05 06:44 [medline]
PHST- 2023/10/05 06:43 [pubmed]
PHST- 2023/10/05 04:09 [entrez]
PHST- 2023/09/19 00:00 [pmc-release]
AID - 10.3389/fmicb.2023.1254342 [doi]
PST - epublish
SO  - Front Microbiol. 2023 Sep 19;14:1254342. doi: 10.3389/fmicb.2023.1254342. 
      eCollection 2023.