Host immune response in Salmonella carriers
Abstract/Contents
- Abstract
- Host-adapted pathogens depend on their host for transmission and dissemination to new hosts. Salmonella enterica includes a plethora of serovars that cause host-adapted diseases in both livestock animals and humans, an example of which is Salmonella enterica serovar Typhi, the causative agent of typhoid fever. Epidemiological and mathematical modeling data indicate that a specific subset of infected hosts are responsible for the majority of disease transmission. Human typhoid carriers are a classic example of this subset, characterized by persistently infected yet asymptomatic individuals who transmit disease via the fecal oral route. The work contained in this thesis attempts to answer how carriers differ from other hosts, in particular how the host immune response in carriers allows those individuals to remain asymptomatic despite the large numbers of Salmonella in the gastrointestinal tract. We use a mouse model of persistent Salmonella infection wherein a subset of the infected hosts (super-shedders) are able to transmit disease to naive cage mates. Having characterized the development of the host immune response during chronic Salmonella infection, we identify an immune state unique to super-shedder hosts. The super-shedder immune phenotype consists of an active innate immune response with high frequency of neutrophils and serum Interleukin-6 and a suppressed adaptive T cell response with dampened cytokine responsiveness. Administration of Granulocyte colony stimulating factor to moderate-shedders is sufficient to phenocopy the blunted T cell responses of the super-shedder immune state demonstrating that neutrophils control the suppression of the adaptive T cell response. The super-shedder immune state also serves a functional purpose, protecting the host against antibiotic-driven dysbiosis. The microbiota and host-pathogen interactions together induce a unique state of tolerance in Salmonella carriers, potentially contributing to the transmission of the pathogen in the general population.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2013 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Gopinath, Smita |
|---|---|
| Associated with | Stanford University, Department of Microbiology and Immunology. |
| Primary advisor | Monack, Denise M |
| Thesis advisor | Monack, Denise M |
| Thesis advisor | Chien, Yueh-Hsiu |
| Thesis advisor | Falkow, Stanley |
| Thesis advisor | Galli, Stephen J |
| Thesis advisor | Sonnenburg, Justin, 1973- |
| Advisor | Chien, Yueh-Hsiu |
| Advisor | Falkow, Stanley |
| Advisor | Galli, Stephen J |
| Advisor | Sonnenburg, Justin, 1973- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Smita Gopinath. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2013. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2013 by Smita Gopinath
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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