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Mast cells: innate attractors recruiting protective CD8 T cells to sites of cytomegalovirus infection

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Abstract

Reactivation of latent cytomegalovirus (CMV) in the transient immunocompromised state after hematoablative treatment is a major concern in patients undergoing hematopoietic cell transplantation (HCT) as a therapy of hematopoietic malignancies. Timely reconstitution of antiviral CD8 T cells and their efficient recruitment to the lungs is crucial for preventing interstitial pneumonia, the most severe disease manifestation of CMV in HCT recipients. Here, we review recent work in a murine model, implicating mast cells (MC) in the control of pulmonary infection. Murine CMV (mCMV) productively infects MC in vivo and triggers their degranulation, resulting in the release of the CC chemokine ligand 5 (CCL5) that attracts CD8 T cells to infiltrate infected tissues. Comparing infection of MC-sufficient C57BL/6 mice and congenic MC-deficient Kit W-sh/W-sh “sash” mutants revealed an inverse relation between the number of lung-infiltrating CD8 T cells and viral burden in the lungs. Specifically, reduced lung infiltration by CD8 T cells in “sash” mutants was associated with an impaired infection control. The causal, though indirect, involvement of MC in antiviral control was confirmed by reversion of the deficiency phenotype in “sash” mutants reconstituted with MC. These recent findings predict that efficient MC reconstitution facilitates the control of CMV infection also in immunocompromised HCT recipients.

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Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft, Clinical Research Group KFO 183 (S.E., M.J.R., and N.A.W.) and Priority Program SPP1394, individual project STA 984/4-1 (MS). NAWL received intramural funding from the young investigator program MAIFOR of the University Medical Center Mainz.

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Author notes

  1. Stefan Ebert

    Present address: Section for Experimental Tumor Immunology, Department for Obstetrics and Gynaecology, University of Wuerzburg Medical School, Würzburg, Germany

  2. Marc Becker

    Present address: Department of Internal Medicine V - Pulmonology, Allergology and Critical Care Medicine, Saarland University Medical Center, Homburg, Saar, Germany

Authors and Affiliations

  1. Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz and Research Center for Immunotherapy (FZI), Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131, Mainz, Germany

    Jürgen Podlech, Stefan Ebert, Matthias J. Reddehase & Niels A. W. Lemmermann

  2. Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz and Research Center for Immunotherapy (FZI), Mainz, Germany

    Marc Becker & Michael Stassen

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  1. Jürgen Podlech
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  2. Stefan Ebert
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  3. Marc Becker
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  4. Matthias J. Reddehase
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  6. Niels A. W. Lemmermann
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Correspondence to Niels A. W. Lemmermann.

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This article is part of the Special Issue on Cytomegalovirus.

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Podlech, J., Ebert, S., Becker, M. et al. Mast cells: innate attractors recruiting protective CD8 T cells to sites of cytomegalovirus infection. Med Microbiol Immunol 204, 327–334 (2015). https://doi.org/10.1007/s00430-015-0386-1

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