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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Microbial Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1439971

Hepatic and Pulmonary Macrophage Activity in a Mucosal Challenge Model of Ebola Virus Disease

Provisionally accepted
Timothy Wanninger Timothy Wanninger 1*Omar A. Saldarriaga Omar A. Saldarriaga 1Esteban Arroyave Esteban Arroyave 1Daniel E. Millian Daniel E. Millian 1Jason Comer Jason Comer 2Slobodan Paessler Slobodan Paessler 1Heather L. Stevenson Heather L. Stevenson 1
  • 1 University of Texas Medical Branch at Galveston, Galveston, United States
  • 2 Louisiana State University Health Shreveport, Shreveport, Louisiana, United States

The final, formatted version of the article will be published soon.

    The inflammatory macrophage response in Ebola virus disease is thought to contribute to severe disease, with liver and lung injury in humans. We sought to further define the activation status of hepatic and pulmonary macrophage populations in Ebola virus disease by comparing liver and lung tissue from terminal Ebola virus (EBOV)-infected and uninfected control cynomolgus macaques challenged via the conjunctival route. Gene and protein expression was quantified using the nCounter and GeoMx Digital Spatial Profiling platforms. Macrophage phenotypes were further quantified by digital pathology analysis. Hepatic macrophages in the EBOV-infected group demonstrated a mixed inflammatory/non-inflammatory profile, with no differences in M1/M2 gene expression compared to controls. Upregulation of CD163, a protein associated with macrophage activation syndrome, was observed in this population. Hepatic macrophages also showed differential expression of monocyte/macrophage differentiation, antigen presentation, and T cell activation gene sets, which were associated with decreased MHC-II allele expression. Moreover, hepatic macrophages had enriched expression of genes and proteins targetable with known immunomodulatory therapeutics, including S100A9, IDO1, and CTLA-4. The significant changes that occurred in both the liver and lung were more pronounced in the liver. These data demonstrate that hepatic macrophages in terminal conjunctivally challenged cynomolgus macaques may express a unique inflammatory profile compared to other macaque models and that macrophage-related pharmacologically druggable targets are expressed in both the liver and the lung in Ebola virus disease.

    Keywords: Ebola, macaque, macrophage, Liver, Lung, CD163, IDO1, MAC387

    Received: 28 May 2024; Accepted: 26 Sep 2024.

    Copyright: © 2024 Wanninger, Saldarriaga, Arroyave, Millian, Comer, Paessler and Stevenson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Timothy Wanninger, University of Texas Medical Branch at Galveston, Galveston, United States

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