| Autor: |
Lecoeur, Hervé, Prina, Eric, Rosazza, Thibault, Kokou, Kossiwa, N’Diaye, Paya, Aulner, Nathalie, Varet, Hugo, Bussotti, Giovanni, Xing, Yue, Milon, Geneviève, Weil, Robert, Meng, Guangxun, Späth, Gerald F. |
| Zdroj: |
Cell Reports; February 2020, Vol. 30 Issue: 6 p1870-1882.e4 |
| Abstrakt: |
Aberrant macrophage activation during intracellular infection generates immunopathologies that can cause severe human morbidity. A better understanding of immune subversion strategies and macrophage phenotypic and functional responses is necessary to design host-directed intervention strategies. Here, we uncover a fine-tuned transcriptional response that is induced in primary and lesional macrophages infected by the parasite Leishmania amazonensisand dampens NF-κB and NLRP3 inflammasome activation. Subversion is amastigote-specific and characterized by a decreased expression of activating and increased expression of de-activating components of these pro-inflammatory pathways, thus revealing a regulatory dichotomy that abrogates the anti-microbial response. Changes in transcript abundance correlate with histone H3K9/14 hypoacetylation and H3K4 hypo-trimethylation in infected primary and lesional macrophages at promoters of NF-κB-related, pro-inflammatory genes. Our results reveal a Leishmaniaimmune subversion strategy targeting host cell epigenetic regulation to establish conditions beneficial for parasite survival and open avenues for host-directed, anti-microbial drug discovery. |
| Databáze: |
Supplemental Index |
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