Life-long control of cytomegalovirus (CMV) by T resident memory cells in the adipose tissue results in inflammation and hyperglycemia
AuthorContreras, Nico A
Sitnik, Katarzyna M
Coplen, Christopher Patrick
AffiliationUniv Arizona, Coll Med Tucson, Dept Immunobiol
Univ Arizona, Ctr Aging, Coll Med
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationContreras NA, Sitnik KM, Jeftic I, Coplen CP, Čičin-Sˇain L, Nikolich-Zˇugich J (2019) Lifelong control of cytomegalovirus (CMV) by T resident memory cells in the adipose tissue results in inflammation and hyperglycemia. PLoS Pathog 15(6): e1007890. https://doi.org/10.1371/journal.ppat.1007890
RightsCopyright © 2019 Contreras et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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AbstractCytomegalovirus (CMV) is a ubiquitous herpesvirus infecting most of the world’s population. CMV has been rigorously investigated for its impact on lifelong immunity and potential complications arising from lifelong infection. A rigorous adaptive immune response mounts during progression of CMV infection from acute to latent states. CD8 T cells, in large part, drive this response and have very clearly been demonstrated to take up residence in the salivary gland and lungs of infected mice during latency. However, the role of tissue resident CD8 T cells as an ongoing defense mechanism against CMV has not been studied in other anatomical locations. Therefore, we sought to identify additional locations of anti-CMV T cell residency and the physiological consequences of such a response. Through RT-qPCR we found that mouse CMV (mCMV) infected the visceral adipose tissue and that this resulted in an expansion of leukocytes in situ. We further found, through flow cytometry, that adipose tissue became enriched in cytotoxic CD8 T cells that are specific for mCMV antigens from day 7 post infection through the lifespan of an infected animal (> 450 days post infection) and that carry markers of tissue residence. Furthermore, we found that inflammatory cytokines are elevated alongside the expansion of CD8 T cells. Finally, we show a correlation between the inflammatory state of adipose tissue in response to mCMV infection and the development of hyperglycemia in mice. Overall, this study identifies adipose tissue as a location of viral infection leading to a sustained and lifelong adaptive immune response mediated by CD8 T cells that correlates with hyperglycemia. These data potentially provide a mechanistic link between metabolic syndrome and chronic infection.
NoteOpen access journal
VersionFinal published version
SponsorsNational Institute on Aging, NIH (USPHS) [AG020179, AG048021]; Bowman Professorship in Medical Science; National Institute of Allergy and Infectious Diseases, NIH [F31AI131622]; European Commission 
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