Moyo, Daniel, Beattie, Lynette, Andrews, Paul Simon et al. (6 more authors) (2018) Macrophage transactivation for chemokine production identified as a negative regulator of granulomatous inflammation using agent-based modeling. Frontiers in immunology. 637. ISSN 1664-3224
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.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2018 Moyo, Beattie, Andrews, Moore, Timmis, Sawtell, Hoehme, Sampson and Kay. |
Dates: |
|
Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Computer Science (York) The University of York > Faculty of Sciences (York) > Centre for Immunology and Infection (CII) (York) The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 15 Mar 2018 10:50 |
Last Modified: | 11 Jan 2025 00:05 |
Published Version: | https://doi.org/10.3389/fimmu.2018.00637 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.3389/fimmu.2018.00637 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:128518 |
Downloads
Filename: Paul_Kaye_Moyo_et_al_Frontiers_342568_complete_author_submitted_manuscript.pdf
Description: Frontiers_342568_complete author submitted manuscript