Mast cells expedite control of pulmonary murine cytomegalovirus infection by enhancing the recruitment of protective CD8 T cells to the lungs.
The lungs are a noted predilection site of acute, latent, and reactivated cytomegalovirus (CMV) infections. Interstitial pneumonia is the most dreaded manifestation of CMV disease in the immunocompromised host, whereas in the immunocompetent host lung-infiltrating CD8 T cells confine the infection in nodular inflammatory foci and prevent viral pathology. By using murine CMV infection as a model, we provide evidence for a critical role of mast cells (MC) in the recruitment of protective CD8 T cells to the lungs. Systemic infection triggered degranulation selectively in infected MC. The viral activation of MC was associated with a wave of CC chemokine ligand 5 (CCL5) in the serum of C57BL/6 mice that was MC-derived as verified by infection of MC-deficient Kit(W-sh/W-sh) "sash" mutants. In these mutants, CD8 T cells were recruited less efficiently to the lungs, correlating with enhanced viral replication and delayed virus clearance. A causative role for MC was verified by MC reconstitution of "sash" mice restoring both, efficient CD8 T-cell recruitment and infection control. These results reveal a novel crosstalk axis between innate and adaptive immune defense against CMV, and identify MC as a hitherto unconsidered player in the immune surveillance at a relevant site of CMV disease.
Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Stefan
S
Ebert
Institute for Immunology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Marc
M
Becker
Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Niels A W
NA
Lemmermann
Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Julia K
JK
Büttner
Institute for Immunology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Anastasija
A
Michel
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Christian
C
Taube
Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Jürgen
J
Podlech
Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Verena
V
Böhm
Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Kirsten
K
Freitag
Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Doris
D
Thomas
Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Rafaela
R
Holtappels
Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Matthias J
MJ
Reddehase
Institute for Immunology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Michael
M
Stassen
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D018146:Muromegalovirus / Q000276:immunology* / Q000378:metabolism; D011024:Pneumonia, Viral / Q000235:genetics / Q000276:immunology* / Q000473:pathology