Neisseria gonorrhoeae modulates epithelial cell responses via the induction and release of the inhibitor of apoptosis protein cIAP2 in exosomes

Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. Previous studies have demonstrated that the sexually transmitted pathogen, Neisseria gonorrhoeae, can induce or inhibit host cell death. N. gonorrhoeae is a mucosal pathogen and, in females, initiates...

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Main Author: Nudel, Kathleen
Language:en_US
Published: 2016
Subjects:
IAP
Online Access:https://hdl.handle.net/2144/14593
id ndltd-bu.edu-oai-open.bu.edu-2144-14593
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spelling ndltd-bu.edu-oai-open.bu.edu-2144-145932019-06-08T03:02:23Z Neisseria gonorrhoeae modulates epithelial cell responses via the induction and release of the inhibitor of apoptosis protein cIAP2 in exosomes Nudel, Kathleen Immunology IAP Neisseria gonorrhoeae Cell death Epithelial cell Exosome Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. Previous studies have demonstrated that the sexually transmitted pathogen, Neisseria gonorrhoeae, can induce or inhibit host cell death. N. gonorrhoeae is a mucosal pathogen and, in females, initiates infection in epithelial cells of the ectocervix and endocervix. Mucosal epithelial cells of the female genital tract are the first line of defense, and thus their cellular fate can alter the early immune response to invading pathogens such as N. gonorrhoeae. The mechanisms by which N. gonorrhoeae modulates cell death are not clear, although a role for the inhibitor of apoptosis-2 (cIAP2) has been proposed. In the present study, we demonstrate that N. gonorrhoeae stimulation induces a transient increase in cIAP2 protein levels in human cervical epithelial cells. High intracellular protein levels were observed during early N. gonorrhoeae stimulation and were followed by a marked intracellular decrease at 24 h. At this time point, we observed increased levels of extracellular cIAP2 associated with exosomes, which are nano-sized vesicles that carry protein and coding RNA as cargo from one cell to another. We also observed that depletion of cIAP2 in N. gonorrhoeae stimulated cells resulted in cell death resembling necroptosis, an inflammatory form of cell death. Furthermore, inhibition of cIAP2 led to an increase in interleukin-1β production. Exosomes have been found to have important roles in cell communication during microbial infection. Here, we demonstrate that N. gonorrhoeae induces exosome production and alters exosome content. We also demonstrate that exosomes elicit cytokine responses in uninfected naïve cells. Collectively, these studies highlight an additional mechanism for epithelial cells to orchestrate the immune response in the female genital tract during N. gonorrhoeae infection. 2016-02-25T14:14:18Z 2016-02-25T14:14:18Z 2016 2016-02-17T20:19:58Z Thesis/Dissertation https://hdl.handle.net/2144/14593 en_US
collection NDLTD
language en_US
sources NDLTD
topic Immunology
IAP
Neisseria gonorrhoeae
Cell death
Epithelial cell
Exosome
spellingShingle Immunology
IAP
Neisseria gonorrhoeae
Cell death
Epithelial cell
Exosome
Nudel, Kathleen
Neisseria gonorrhoeae modulates epithelial cell responses via the induction and release of the inhibitor of apoptosis protein cIAP2 in exosomes
description Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. Previous studies have demonstrated that the sexually transmitted pathogen, Neisseria gonorrhoeae, can induce or inhibit host cell death. N. gonorrhoeae is a mucosal pathogen and, in females, initiates infection in epithelial cells of the ectocervix and endocervix. Mucosal epithelial cells of the female genital tract are the first line of defense, and thus their cellular fate can alter the early immune response to invading pathogens such as N. gonorrhoeae. The mechanisms by which N. gonorrhoeae modulates cell death are not clear, although a role for the inhibitor of apoptosis-2 (cIAP2) has been proposed. In the present study, we demonstrate that N. gonorrhoeae stimulation induces a transient increase in cIAP2 protein levels in human cervical epithelial cells. High intracellular protein levels were observed during early N. gonorrhoeae stimulation and were followed by a marked intracellular decrease at 24 h. At this time point, we observed increased levels of extracellular cIAP2 associated with exosomes, which are nano-sized vesicles that carry protein and coding RNA as cargo from one cell to another. We also observed that depletion of cIAP2 in N. gonorrhoeae stimulated cells resulted in cell death resembling necroptosis, an inflammatory form of cell death. Furthermore, inhibition of cIAP2 led to an increase in interleukin-1β production. Exosomes have been found to have important roles in cell communication during microbial infection. Here, we demonstrate that N. gonorrhoeae induces exosome production and alters exosome content. We also demonstrate that exosomes elicit cytokine responses in uninfected naïve cells. Collectively, these studies highlight an additional mechanism for epithelial cells to orchestrate the immune response in the female genital tract during N. gonorrhoeae infection.
author Nudel, Kathleen
author_facet Nudel, Kathleen
author_sort Nudel, Kathleen
title Neisseria gonorrhoeae modulates epithelial cell responses via the induction and release of the inhibitor of apoptosis protein cIAP2 in exosomes
title_short Neisseria gonorrhoeae modulates epithelial cell responses via the induction and release of the inhibitor of apoptosis protein cIAP2 in exosomes
title_full Neisseria gonorrhoeae modulates epithelial cell responses via the induction and release of the inhibitor of apoptosis protein cIAP2 in exosomes
title_fullStr Neisseria gonorrhoeae modulates epithelial cell responses via the induction and release of the inhibitor of apoptosis protein cIAP2 in exosomes
title_full_unstemmed Neisseria gonorrhoeae modulates epithelial cell responses via the induction and release of the inhibitor of apoptosis protein cIAP2 in exosomes
title_sort neisseria gonorrhoeae modulates epithelial cell responses via the induction and release of the inhibitor of apoptosis protein ciap2 in exosomes
publishDate 2016
url https://hdl.handle.net/2144/14593
work_keys_str_mv AT nudelkathleen neisseriagonorrhoeaemodulatesepithelialcellresponsesviatheinductionandreleaseoftheinhibitorofapoptosisproteinciap2inexosomes
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