Molecular mechanisms underlying glial inflammatory responses to Neisseria meningitidis

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Davis, E. (2022). Molecular mechanisms underlying glial inflammatory responses to Neisseria meningitidis. Unc Charlotte Undergraduate Research Conference.
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Over 1.2 million cases of bacterial meningitis occur worldwide each year. The bacterial pathogen Neisseria meningitidis (Nm) is the leading cause of pyogenic and epidemic meningitis, a life-threatening condition with a 15% mortality rate. Additionally, up to 20% of survivors suffer long-term central nervous system (CNS) deficits due to severe neuroinflammation. Within the CNS, microglia and astrocytes are cells crucial to the initiation and regulation of these immune responses to bacterial infections. Our lab and others have demonstrated both microglia and astrocytes rapidly release proinflammatory cytokines followed by later production of anti-inflammatory cytokines in response to Nm challenge. Intriguingly, Nm has been reported to bind and import host cytokines that then drive changes in bacterial gene expression, suggesting that cytokine responses serve as environmental cues to promote virulence. This study begins to address the hypothesis that Nm pathogen-associated molecular patterns (PAMPs) initiate glial immune responses that, in turn, regulate bacterial gene expression to further exacerbate infection. Nm was grown to mid-log phase in the absence or presence of host inflammatory cytokines TNF, IL-6, and IL-1β, or anti-inflammatory cytokines IL-10 and IL-19. An RNA sequencing approach was used to compare differences in transcriptome-wide gene expression profiles for Nm. These pilot studies are an essential first step in dissecting the intimate relationship between Nm and glial cells that underlies the development of detrimental neuroinflammation. Future studies will confirm novel gene clusters or molecular pathways and genes associated with Nm immune stimulation and evasion. Presented at the 2022 UNC Charlotte Undergraduate Research Conference.

Details
Title

Molecular mechanisms underlying glial inflammatory responses to Neisseria meningitidis

Author(s)

Davis, Erin

UNC Charlotte Affiliate Type

Undergraduate

Extent

1 online resource

Date Created

2022

Material Type

Conference poster

Genre

conference proceedings

Resource Type

text

Abstract

Over 1.2 million cases of bacterial meningitis occur worldwide each year. The bacterial pathogen Neisseria meningitidis (Nm) is the leading cause of pyogenic and epidemic meningitis, a life-threatening condition with a 15% mortality rate. Additionally, up to 20% of survivors suffer long-term central nervous system (CNS) deficits due to severe neuroinflammation. Within the CNS, microglia and astrocytes are cells crucial to the initiation and regulation of these immune responses to bacterial infections. Our lab and others have demonstrated both microglia and astrocytes rapidly release proinflammatory cytokines followed by later production of anti-inflammatory cytokines in response to Nm challenge. Intriguingly, Nm has been reported to bind and import host cytokines that then drive changes in bacterial gene expression, suggesting that cytokine responses serve as environmental cues to promote virulence. This study begins to address the hypothesis that Nm pathogen-associated molecular patterns (PAMPs) initiate glial immune responses that, in turn, regulate bacterial gene expression to further exacerbate infection. Nm was grown to mid-log phase in the absence or presence of host inflammatory cytokines TNF, IL-6, and IL-1β, or anti-inflammatory cytokines IL-10 and IL-19. An RNA sequencing approach was used to compare differences in transcriptome-wide gene expression profiles for Nm. These pilot studies are an essential first step in dissecting the intimate relationship between Nm and glial cells that underlies the development of detrimental neuroinflammation. Future studies will confirm novel gene clusters or molecular pathways and genes associated with Nm immune stimulation and evasion. Presented at the 2022 UNC Charlotte Undergraduate Research Conference.

Subjects--Topics

Meningitis
Immune response

Is Part Of

UNC Charlotte undergraduate research conference

Language

English

Permalink

http://hdl.handle.net/20.500.13093/work:288

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