Skip to main content
Duke University Libraries
DukeSpace Scholarship by Duke Authors
  • Login
  • Ask
  • Menu
  • Login
  • Ask a Librarian
  • Search & Find
  • Using the Library
  • Research Support
  • Course Support
  • Libraries
  • About
View Item 
  •   DukeSpace
  • Theses and Dissertations
  • Duke Dissertations
  • View Item
  •   DukeSpace
  • Theses and Dissertations
  • Duke Dissertations
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Salmonella Suppress Innate Immunity by Targeting Mast Cells

Thumbnail
View / Download
5.9 Mb
Date
2014
Author
Choi, Hae Woong
Advisor
Abraham, Soman N.
Repository Usage Stats
356
views
417
downloads
Abstract

Mast cells (MCs) are increasingly recognized as powerful sentinel cells responsible for modulating the early immune responses to a wide range of infectious agents. This protective role is attributable in part to their preponderance at the host-environment interface and their innate capacity to rapidly release modulators of immune cell trafficking which promotes the early recruitment of pathogen-clearing immune cells from the blood. However, host-adapted pathogens had been a critical threat to human for a long time because they have evolved mechanisms directed at overcoming protective immunity.

In this work, we outline <italic>Salmonella enterica</italic> serovar Typhimurium has evolved a novel mechanism to inactivate peripheral MCs resulting in limited neutrophil responses at infection sites in early stage of infection. Because of the delay in bacterial clearance at the point of entry, <italic>Salmonella</italic> are able to multiply and rapidly disseminate to distal sites. Suppression of local MCs' degranulation restricted outflow of vascular contents into infection sites, thus facilitating bacterial spread.

We discover MC suppression is mediated by the Salmonella Protein Tyrosine Phosphatase (SptP), which shares structural homology with <italic>Yersinia</italic> YopH. Interestingly, SptP, not only shares homology with phosphatases found in MCs, they are also homologous to YopH an effector protein expressed by plague causing <italic>Yersinia pestis</italic>. We show that YopH had MC suppressing abilities as SptP suggesting that this activity is shared among some of the more virulent bacterial pathogens. The functionally relevant domain in SptP is its enzymatic site and that it works by dephosphorylating the vesicle fusion protein N-ethylmalemide-sensitive factor (NSF) and by blocking phosphorylation of Syk, which is located in downstream and upstream of tyrosine phosphorylation signaling pathway in MCs.

Without SptP, orally challenged <italic>S.</italic> Typhimurium failed to suppress MC degranulation and exhibited limited colonization of the mesenteric lymph nodes. Administration of SptP to sites of Escherichia coli infection markedly enhanced its virulence. Thus, SptP-mediated inactivation of local MCs is a powerful mechanism utilized by <italic>S.</italic> Typhimurium to impede early innate immunity. This finding provides a logical explanation for why previous attempts by others to demonstrate a protective role for MCs against <italic>Salmonella</italic> infections have resulted in equivocal results.

Taken together, this work highlights an overlooked virulence mechanism possessed by certain host adapted pathogens to avoid the host's innate immune system. Additionally, this innate immune-quelling property of SptP may hold future promise in tempering harmful inflammatory disorders in the body of an immune competent host.

Type
Dissertation
Department
Pathology
Subject
Immunology
Microbiology
Degranulation
Innate Immunity
Mast cell
Salmonella Typhimurium
SptP
Suppression
Permalink
https://hdl.handle.net/10161/8704
Citation
Choi, Hae Woong (2014). Salmonella Suppress Innate Immunity by Targeting Mast Cells. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/8704.
Collections
  • Duke Dissertations
More Info
Show full item record
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.

Rights for Collection: Duke Dissertations


Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info

Make Your Work Available Here

How to Deposit

Browse

All of DukeSpaceCommunities & CollectionsAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit DateThis CollectionAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit Date

My Account

LoginRegister

Statistics

View Usage Statistics
Duke University Libraries

Contact Us

411 Chapel Drive
Durham, NC 27708
(919) 660-5870
Perkins Library Service Desk

Digital Repositories at Duke

  • Report a problem with the repositories
  • About digital repositories at Duke
  • Accessibility Policy
  • Deaccession and DMCA Takedown Policy

TwitterFacebookYouTubeFlickrInstagramBlogs

Sign Up for Our Newsletter
  • Re-use & Attribution / Privacy
  • Harmful Language Statement
  • Support the Libraries
Duke University