PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.
Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-07-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1005739 |
| _version_ | 1819133127012909056 |
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| author | Philana Ling Lin Pauline Maiello Hannah P Gideon M Teresa Coleman Anthony M Cadena Mark A Rodgers Robert Gregg Melanie O'Malley Jaime Tomko Daniel Fillmore L James Frye Tara Rutledge Robert M DiFazio Christopher Janssen Edwin Klein Peter L Andersen Sarah M Fortune JoAnne L Flynn |
| author_facet | Philana Ling Lin Pauline Maiello Hannah P Gideon M Teresa Coleman Anthony M Cadena Mark A Rodgers Robert Gregg Melanie O'Malley Jaime Tomko Daniel Fillmore L James Frye Tara Rutledge Robert M DiFazio Christopher Janssen Edwin Klein Peter L Andersen Sarah M Fortune JoAnne L Flynn |
| author_sort | Philana Ling Lin |
| collection | DOAJ |
| description | Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT) of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF) neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26) before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25). Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection. |
| first_indexed | 2024-12-22T09:42:21Z |
| format | Article |
| id | doaj.art-618e2e8d7ad5407fae0a0f8a69153c72 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-22T09:42:21Z |
| publishDate | 2016-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-618e2e8d7ad5407fae0a0f8a69153c722022-12-21T18:30:38ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-07-01127e100573910.1371/journal.ppat.1005739PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.Philana Ling LinPauline MaielloHannah P GideonM Teresa ColemanAnthony M CadenaMark A RodgersRobert GreggMelanie O'MalleyJaime TomkoDaniel FillmoreL James FryeTara RutledgeRobert M DiFazioChristopher JanssenEdwin KleinPeter L AndersenSarah M FortuneJoAnne L FlynnMycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT) of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF) neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26) before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25). Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection.https://doi.org/10.1371/journal.ppat.1005739 |
| spellingShingle | Philana Ling Lin Pauline Maiello Hannah P Gideon M Teresa Coleman Anthony M Cadena Mark A Rodgers Robert Gregg Melanie O'Malley Jaime Tomko Daniel Fillmore L James Frye Tara Rutledge Robert M DiFazio Christopher Janssen Edwin Klein Peter L Andersen Sarah M Fortune JoAnne L Flynn PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis. PLoS Pathogens |
| title | PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis. |
| title_full | PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis. |
| title_fullStr | PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis. |
| title_full_unstemmed | PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis. |
| title_short | PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis. |
| title_sort | pet ct identifies reactivation risk in cynomolgus macaques with latent m tuberculosis |
| url | https://doi.org/10.1371/journal.ppat.1005739 |
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