Virus-associated Inflammation Imprints an Inflammatory Profile on Long-lived Monocyte-derived Macrophages in the Human Liver

Sanchez, J.-D.; Nkongolo, S.; Traum, D.; Kim, S. C.; Mahamed, D.; Mehrotra, A.; Patel, A.; Chen, D.; Fung, S.; Gaggar, A.; Feld, J. J.; Chang, K.-M.; Wallin, J. J.; Janssen, H. L. A.; Gehring, A. J.

doi:10.1101/2024.01.31.578178

bioRxiv · 10.1101/2024.01.31.578178

Virus-associated Inflammation Imprints an Inflammatory Profile on Long-lived Monocyte-derived Macrophages in the Human Liver

Sanchez, J.-D.·Nkongolo, S.·Traum, D.·Kim, S. C.·Mahamed, D.·Mehrotra, A.·Patel, A.·Chen, D.·Fung, S.·Gaggar, A.·Feld, J. J.·Chang, K.-M.·Wallin, J. J.·Janssen, H. L. A.·Gehring, A. J.

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Abstract

Chronic liver injury triggers the activation and recruitment of immune cells, causing antigen-independent tissue damage and liver disease progression. Tissue inflammation can reshape macrophage composition through monocyte replacement. Replacement of tissue macrophages with monocytes differentiating in an inflammatory environment can potentially imprint a phenotype that switches the liver from an immunotolerant organ to one predisposed to tissue damage. We longitudinally sampled the liver of chronic hepatitis B (CHB) patients with active liver inflammation starting antiviral therapy. Antiviral therapy suppressed viral replication and liver inflammation, which coincided with decreased myeloid activation markers. Single-cell RNA sequencing mapped peripheral inflammatory markers to a monocyte-derived macrophage population, distinct from Kupffer cells, with an inflammatory transcriptional profile. The inflammatory macrophages (iMacs) differentiated from blood monocytes and established a long-lived population. The iMacs retained their core transcriptional signature, consistent with trained immunity, resulting in a population of macrophages primed for inflammation potentially driving progressive liver disease.

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Sanchez, J.-D., Nkongolo, S., Traum, D., Kim, S. C., Mahamed, D., Mehrotra, A., Patel, A., Chen, D., Fung, S., Gaggar, A., Feld, J. J., Chang, K.-M., Wallin, J. J., Janssen, H. L. A., Gehring, A. J.. 2024-01-31. Virus-associated Inflammation Imprints an Inflammatory Profile on Long-lived Monocyte-derived Macrophages in the Human Liver. https://doi.org/10.1101/2024.01.31.578178

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