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Front. Immunol. | doi: 10.3389/fimmu.2019.01247

CD49a expression identifies a subset of intrahepatic macrophages in humans

 Gloria Martrus1,  Hanna Goebels1, Annika E. Langeneckert1, Janine Kah2,  Felix Flomm1, Wilhelm Salzberger1, Leonard U. Hess1, Annerose E. Ziegler1, Tobias Poch2,  Björn Nashan2, Christoph Schramm2, Karl J. Oldhafer3, Maura Dandri2, Martina Koch2, Sebastian Lunemann1 and  Marcus Altfeld1*
  • 1Heinrich Pette Institut, Leibniz-Institut für Experimentelle Virologie, Germany
  • 2University Medical Center Hamburg-Eppendorf, Germany
  • 3Asklepios Klinik Barmbek, Germany

Macrophages play central roles in inflammatory reactions and initiation of immune responses during infections. More than 80% of total tissue macrophages are described to be located in the liver as liver-derived macrophages, also named Kupffer cells (KCs). While studies in mice have established a central role of liver-resident KCs in regulating liver inflammation, their phenotype and function are not well characterized in humans. Comparing paired human liver and peripheral blood samples, we observed significant differences in the distribution of macrophage (Mφ) subsets, with lower frequencies of CD14hiCD16lo and higher frequencies of CD14int-hiCD16int Mφ in human livers. Intrahepatic Mφ consisted of diverse subsets with differential expression of CD49a, a liver-residency marker previously described for human and mice NK cells, and VSIG4 and/or MARCO, two recently described human tissue Mφ markers. Furthermore, intrahepatic CD49a+ Mφ expressed significantly higher levels of maturation and activation markers, exhibited higher baseline levels of TNF-α, IL-12 and IL-10 production, but responded less to additional in vitro TLR stimulation. In contrast, intrahepatic CD49a- Mφ were highly responsive to stimulation with TLR ligands, similar to what was observed for CD49a- monocytes (MOs) in peripheral blood. Taken together, these studies identified populations of CD49a+, VSIG4+ and/or MARCO+ Mφ in human livers, and demonstrated that intrahepatic CD49a+ Mφ differed in phenotype and function from intrahepatic CD49a- Mφ as well as from peripheral blood-derived monocytes.

Keywords: macrophage, tissue residency, human liver, Cell activation, CD49a

Received: 11 Dec 2018; Accepted: 16 May 2019.

Edited by:

Simon Yona, University College London, United Kingdom

Reviewed by:

Ehud Zigmond, Tel Aviv Sourasky Medical Center, Israel
Prakash Ramachandran, University of Edinburgh, United Kingdom  

Copyright: © 2019 Martrus, Goebels, Langeneckert, Kah, Flomm, Salzberger, Hess, Ziegler, Poch, Nashan, Schramm, Oldhafer, Dandri, Koch, Lunemann and Altfeld. 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) and the copyright owner(s) 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: Prof. Marcus Altfeld, Heinrich Pette Institut, Leibniz-Institut für Experimentelle Virologie, Hamburg, Germany,