Immune cell infiltration and modulation of the blood-brain barrier in a guinea pig model of tuberculosis: Observations without evidence of bacterial dissemination to the brain.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is a chronic inflammatory disease. Although typically associated with inflammation of the lungs and other peripheral tissues, increasing evidence has uncovered neurological consequences attributable to Mtb infection. These incl...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0307577 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841555554582921216 |
|---|---|
| author | Amanda S Latham Charlize E Geer David F Ackart Kristin N Weninger Chase C Gross Brendan K Podell Randall J Basaraba Julie A Moreno |
| author_facet | Amanda S Latham Charlize E Geer David F Ackart Kristin N Weninger Chase C Gross Brendan K Podell Randall J Basaraba Julie A Moreno |
| author_sort | Amanda S Latham |
| collection | DOAJ |
| description | Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is a chronic inflammatory disease. Although typically associated with inflammation of the lungs and other peripheral tissues, increasing evidence has uncovered neurological consequences attributable to Mtb infection. These include deficits in memory and cognition, increased risk for neurodegenerative disease, and progressive neuropathology. Although the neurological effects of the disease, without CNS infection, have been characterized, the mechanism of neurotoxicity is unknown. We hypothesized that alterations to the blood-brain barrier (BBB) allows peripheral immune cells to enter the brain, initiating a neuroinflammatory response. To test this hypothesis, guinea pigs were exposed by aerosol to a laboratory and a clinical Mtb strain for 15 days. Following Mtb infection, proteins critical to BBB function, including claudin V and collagen IV, are modulated without evidence of bacterial dissemination to the brain. This is correlated with increased contact of astrocytic processes to vessels in the brain, as well as increased expression of the water channel protein aquaporin 4 (AQP4) on endfeet. Upon further investigation, we discovered the potential role of glial reactivity, which is increased following infection with both bacterial strains, in the progression of BBB changes and, ultimately, the permeability of peripheral immune cells into the brain. Through these data, we have obtained a preliminary understanding of the mechanisms of cellular stress in the brain following pulmonary Mtb infection which should be further investigated in future studies. |
| format | Article |
| id | doaj-art-4ef52534dc624e00820372ec48e97214 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-4ef52534dc624e00820372ec48e972142025-01-08T05:32:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e030757710.1371/journal.pone.0307577Immune cell infiltration and modulation of the blood-brain barrier in a guinea pig model of tuberculosis: Observations without evidence of bacterial dissemination to the brain.Amanda S LathamCharlize E GeerDavid F AckartKristin N WeningerChase C GrossBrendan K PodellRandall J BasarabaJulie A MorenoTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is a chronic inflammatory disease. Although typically associated with inflammation of the lungs and other peripheral tissues, increasing evidence has uncovered neurological consequences attributable to Mtb infection. These include deficits in memory and cognition, increased risk for neurodegenerative disease, and progressive neuropathology. Although the neurological effects of the disease, without CNS infection, have been characterized, the mechanism of neurotoxicity is unknown. We hypothesized that alterations to the blood-brain barrier (BBB) allows peripheral immune cells to enter the brain, initiating a neuroinflammatory response. To test this hypothesis, guinea pigs were exposed by aerosol to a laboratory and a clinical Mtb strain for 15 days. Following Mtb infection, proteins critical to BBB function, including claudin V and collagen IV, are modulated without evidence of bacterial dissemination to the brain. This is correlated with increased contact of astrocytic processes to vessels in the brain, as well as increased expression of the water channel protein aquaporin 4 (AQP4) on endfeet. Upon further investigation, we discovered the potential role of glial reactivity, which is increased following infection with both bacterial strains, in the progression of BBB changes and, ultimately, the permeability of peripheral immune cells into the brain. Through these data, we have obtained a preliminary understanding of the mechanisms of cellular stress in the brain following pulmonary Mtb infection which should be further investigated in future studies.https://doi.org/10.1371/journal.pone.0307577 |
| spellingShingle | Amanda S Latham Charlize E Geer David F Ackart Kristin N Weninger Chase C Gross Brendan K Podell Randall J Basaraba Julie A Moreno Immune cell infiltration and modulation of the blood-brain barrier in a guinea pig model of tuberculosis: Observations without evidence of bacterial dissemination to the brain. PLoS ONE |
| title | Immune cell infiltration and modulation of the blood-brain barrier in a guinea pig model of tuberculosis: Observations without evidence of bacterial dissemination to the brain. |
| title_full | Immune cell infiltration and modulation of the blood-brain barrier in a guinea pig model of tuberculosis: Observations without evidence of bacterial dissemination to the brain. |
| title_fullStr | Immune cell infiltration and modulation of the blood-brain barrier in a guinea pig model of tuberculosis: Observations without evidence of bacterial dissemination to the brain. |
| title_full_unstemmed | Immune cell infiltration and modulation of the blood-brain barrier in a guinea pig model of tuberculosis: Observations without evidence of bacterial dissemination to the brain. |
| title_short | Immune cell infiltration and modulation of the blood-brain barrier in a guinea pig model of tuberculosis: Observations without evidence of bacterial dissemination to the brain. |
| title_sort | immune cell infiltration and modulation of the blood brain barrier in a guinea pig model of tuberculosis observations without evidence of bacterial dissemination to the brain |
| url | https://doi.org/10.1371/journal.pone.0307577 |
| work_keys_str_mv | AT amandaslatham immunecellinfiltrationandmodulationofthebloodbrainbarrierinaguineapigmodeloftuberculosisobservationswithoutevidenceofbacterialdisseminationtothebrain AT charlizeegeer immunecellinfiltrationandmodulationofthebloodbrainbarrierinaguineapigmodeloftuberculosisobservationswithoutevidenceofbacterialdisseminationtothebrain AT davidfackart immunecellinfiltrationandmodulationofthebloodbrainbarrierinaguineapigmodeloftuberculosisobservationswithoutevidenceofbacterialdisseminationtothebrain AT kristinnweninger immunecellinfiltrationandmodulationofthebloodbrainbarrierinaguineapigmodeloftuberculosisobservationswithoutevidenceofbacterialdisseminationtothebrain AT chasecgross immunecellinfiltrationandmodulationofthebloodbrainbarrierinaguineapigmodeloftuberculosisobservationswithoutevidenceofbacterialdisseminationtothebrain AT brendankpodell immunecellinfiltrationandmodulationofthebloodbrainbarrierinaguineapigmodeloftuberculosisobservationswithoutevidenceofbacterialdisseminationtothebrain AT randalljbasaraba immunecellinfiltrationandmodulationofthebloodbrainbarrierinaguineapigmodeloftuberculosisobservationswithoutevidenceofbacterialdisseminationtothebrain AT julieamoreno immunecellinfiltrationandmodulationofthebloodbrainbarrierinaguineapigmodeloftuberculosisobservationswithoutevidenceofbacterialdisseminationtothebrain |