Perturbation of lytic and latent gammaherpesvirus infection in the absence of the inhibitory receptor CEACAM1.
Control of gammaherpesvirus infections requires a complex, well orchestrated immune response regulated by positive and negative co-signaling molecules. While the impact of co-stimulatory molecules has been addressed in various studies, the role of co-inhibitory receptors has not been tested. The ITIM-bearing CEACAM1 is an inhibitory receptor expressed by a variety of immune cells, including B, T and NK cells. Using Ceacam1(-/-) mice, we analyzed the in vivo function of CEACAM1 during acute and latent murine gammaherpesvirus 68 (MHV-68) infection. During acute lytic replication, we observed lower virus titers in the lungs of Ceacam1(-/-) mice than in WT mice. In contrast, during latency amplification, Ceacam1(-/-) mice displayed increased splenomegaly and a higher latent viral load in the spleen. Analysis of the immune response revealed increased virus-specific antibody levels in Ceacam1(-/-) mice, while the magnitude of the T cell-mediated antiviral immune response was reduced. These findings suggest that inhibitory receptors can modulate the efficacy of immune responses against gammaherpesvirus infections.
Adler
Heiko
H
Helmholtz Zentrum München - National Research Center for Environmental Health, Institute of Molecular Immunology, CCG HCT, Munich, Germany.
El-Gogo
Susanne
S
Guggemoos
Simone
S
Zimmermann
Wolfgang
W
Beauchemin
Nicole
N
Kammerer
Robert
R
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D018142:Gammaherpesvirinae / Q000378:metabolism* / Q000502:physiology; D006566:Herpesviridae Infections / Q000276:immunology / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication
D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D015848:Interleukin-5