By the same authors

From the same journal

Macrophage transactivation for chemokine production identified as a negative regulator of granulomatous inflammation using agent-based modeling

Research output: Contribution to journalArticle

Full text download(s)

Published copy (DOI)

Author(s)

Department/unit(s)

Publication details

JournalFrontiers in immunology
DateAccepted/In press - 14 Mar 2018
DatePublished (current) - 27 Mar 2018
Issue number637
Volume9
Number of pages10
Original languageEnglish

Abstract

Cellular activation in trans by interferons, cytokines and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and / or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani-infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous
30 inflammation. We propose trans-activation for chemokine production as a novel
31 broadly applicable mechanism that may operate early in infection to limit excessive
32 focal inflammation.

Bibliographical note

© 2018 Moyo, Beattie, Andrews, Moore, Timmis, Sawtell, Hoehme, Sampson and Kay.

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations