Moyo, Daniel
[Author];
Beattie, Lynette
[Author];
Andrews, Paul S.
[Author];
Moore, John W. J.
[Author];
Timmis, Jon
[Author];
Sawtell, Amy
[Author];
Hoehme, Stefan
[Author];
Sampson, Adam T.
[Author];
Kaye, Paul M.
[Author]
Macrophage Transactivation for chemokine Production identified as a negative regulator of granulomatous inflammation Using agent-Based Modeling
You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Macrophage Transactivation for chemokine Production identified as a negative regulator of granulomatous inflammation Using agent-Based Modeling
Contributor:
Moyo, Daniel
[Author];
Beattie, Lynette
[Author];
Andrews, Paul S.
[Author];
Moore, John W. J.
[Author];
Timmis, Jon
[Author];
Sawtell, Amy
[Author];
Hoehme, Stefan
[Author];
Sampson, Adam T.
[Author];
Kaye, Paul M.
[Author]
imprint:
Lausanne: Frontiers Research Foundation, [2023]
Description:
Cellular activation in trans by interferons, cytokines, and chemokines is a commonlyrecognized mechanism to amplify immune effector function and limit pathogenspread. However, an optimal host response also requires that collateral damageassociated with inflammation is limited. This may be particularly so in the case ofgranulomatous inflammation, where an excessive number and/or excessively floridgranulomas can have significant pathological consequences. Here, we have combinedtranscriptomics, agent-based modeling, and in vivo experimental approaches to studyconstraints on hepatic granuloma formation in a murine model of experimental leishmaniasis.We demonstrate that chemokine production by non-infected Kupffer cellsin the Leishmania donovani-infected liver promotes competition with infected KCs foravailable iNKT cells, ultimately inhibiting the extent of granulomatous inflammation.We propose trans-activation for chemokine production as a novel broadly applicablemechanism that may operate early in infection to limit excessive focal inflammation.