The pathogenesis of persistent infection is dictated by the balance between opposing immune activation and suppression signals. Herein, virulent Salmonella was used to explore the role and potential importance of Foxp3-expressing regulatory T cells in dictating the natural progression of persistent bacterial infection. Two distinct phases of persistent Salmonella infection are identified. In the first 3–4 weeks after infection, progressively increasing bacterial burden was associated with delayed effector T cell activation. Reciprocally, at later time points after infection, reductions in bacterial burden were associated with robust effector T cell activation. Using Foxp3GFP reporter mice for ex vivo isolation of regulatory T cells, we demonstrate that the dichotomy in infection tempo between early and late time points is directly paralleled by drastic changes in Foxp3+ Treg suppressive potency. In complementary experiments using Foxp3DTR mice, the significance of these shifts in Treg suppressive potency on infection outcome was verified by enumerating the relative impacts of regulatory T cell ablation on bacterial burden and effector T cell activation at early and late time points during persistent Salmonella infection. Moreover, Treg expression of CTLA-4 directly paralleled changes in suppressive potency, and the relative effects of Treg ablation could be largely recapitulated by CTLA-4 in vivo blockade. Together, these results demonstrate that dynamic regulation of Treg suppressive potency dictates the course of persistent bacterial infection.

/pdf/regulatory-t-cell-suppressive-potency-dictates-the-balance-5g2lp0sv1k.pdf

Regulatory T Cell Suppressive Potency Dictates the Balance between Bacterial Proliferation and Clearance during Persistent Salmonella Infection

Host cytokine response and resistance to Salmonella infection.

Bacterial virulence, proinflammatory cytokines and host immunity: how to choose the appropriate Salmonella vaccine strain?

Lps- defective C57BL/10ScCr (Cr) mice are homozygous for a deletion encompassing Toll-like receptor 4 that makes them refractory to the biological activity of LPS. In addition, these mice exhibit an inherited IL-12 unresponsiveness resulting in impaired IFN-γ responses to different microorganisms. By positional cloning methods, we show here that this second defect of Cr mice is due to a mutation in a single gene located on mouse chromosome 6, in close proximity to the Igκ locus. The gene is IL-12Rβ2 . Cr mice carry a point mutation creating a stop codon that is predicted to cause premature termination of the translated IL-12Rβ2 after a lysine residue at position 777. The truncated β2 chain can still form a heterodimeric IL-12R that allows phosphorylation of Janus kinase 2, but, unlike the wild-type IL-12R, can no longer mediate phosphorylation of STAT4. Because the phosphorylation of STAT4 is a prerequisite for the IL-12-mediated induction of IFN-γ, its absence in Cr mice is responsible for their defective IFN-γ response to microorganisms.

A point mutation in the IL-12R beta 2 gene underlies the IL-12 unresponsiveness of Lps-defective C57BL/10ScCr mice.

Attenuated Salmonella enterica serovar Typhimurium lacking the ZnuABC transporter confers immune-based protection against challenge infections in mice.

Formation of interferon-γ (IFN-γ) and tumor necrosis factor (TNF) during Salmonella typhimurium infection was investigated in lipopolysaccharide (LPS)-sensitive C3H/HeN and C57BL/10ScSn(B10ScSn), and LPS-resistant (Ipsdmutant) C3H/HeJ and C57BL/10ScCr(B10ScCr) mice. When infected with 50 colony-forming units (CFU) of S. typhimurium C5, C3H/HeN and BlOScSn mice became hypersensitive to the lethal effect of LPS. In the case of Ipsdmutants, only C3H/HeJ mice became hypersensitive to LPS, while BlOScCr mice remained resistant. C3H/HeJ as well as BlOScSn mice produced significant amounts of plasma IFN-γ on day 3 after infection. By this time bacterial CFU in the liver of B10ScSn and C3H/HeJ mice were 106.7 and 107.1, respectively. In B10ScCr mice, however, IFN-γ was not detectable although bacteria present in the liver exceeded 108 CFU. On the other hand, plasma TNF was not detectable in any of the mouse strains during S. typhimurium infection. When S. typhimurium-infected mice were challenged with LPS on day 3, significant amounts of plasma TNF were measured in C3H/HeN and B10ScSn mice, while in the Ipsdmutant C3H/HeJ and B10ScCr mice plasma TNF was undetectable.

Formation of interferon-gamma and tumor necrosis factor in mice during Salmonella typhimurium infection.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

C. Hausmann

Author Tools

Chat about Author

Papers

Formation of interferon-gamma and tumor necrosis factor in mice during Salmonella typhimurium infection.