Cytomegalovirus subverts macrophage identity

Baasch S, Giansanti P, Kolter J, Riedl A, Forde AJ, Runge S, Zenke S, Elling R, Halenius A, Brabletz S, Hengel H, Kuster B, Brabletz T, Cicin-Sain L, Arens R, Vlachos A, Rohr JC, Stemmler M, Kopf M, Ruzsics Z, Henneke P (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cell Elsevier

Book Volume: 184

Pages Range: 3774-3793.e25

Journal Issue: 14

DOI: 10.1016/j.cell.2021.05.009

Abstract

Cytomegaloviruses (CMVs) have co-evolved with their mammalian hosts for millions of years, leading to remarkable host specificity and high infection prevalence. Macrophages, which already populate barrier tissues in the embryo, are the predominant immune cells at potential CMV entry sites. Here we show that, upon CMV infection, macrophages undergo a morphological, immunophenotypic, and metabolic transformation process with features of stemness, altered migration, enhanced invasiveness, and provision of the cell cycle machinery for viral proliferation. This complex process depends on Wnt signaling and the transcription factor ZEB1. In pulmonary infection, mouse CMV primarily targets and reprograms alveolar macrophages, which alters lung physiology and facilitates primary CMV and secondary bacterial infection by attenuating the inflammatory response. Thus, CMV profoundly perturbs macrophage identity beyond established limits of plasticity and rewires specific differentiation processes, allowing viral spread and impairing innate tissue immunity.

Authors with CRIS profile

Simone Brabletz Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung) Thomas Brabletz Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Marc Stemmler Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung

Involved external institutions

Universitätsklinikum Freiburg DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich CH Switzerland (CH) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Leiden University Medical Center NL Netherlands (NL)

How to cite

APA:

Baasch, S., Giansanti, P., Kolter, J., Riedl, A., Forde, A.J., Runge, S.,... Henneke, P. (2021). Cytomegalovirus subverts macrophage identity. Cell, 184(14), 3774-3793.e25. https://doi.org/10.1016/j.cell.2021.05.009

MLA:

Baasch, Sebastian, et al. "Cytomegalovirus subverts macrophage identity." Cell 184.14 (2021): 3774-3793.e25.

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