Subclinical cytomegalovirus infection is associated with altered host immunity, gut microbiota, and vaccine responses

Clarissa Santos Rocha, Lauren A. Hirao, Mariana G. Weber, Gema Méndez-Lagares, W. L. William Chang, Guochun Jiang, Jesse D. Deere, Ellen Elizabeth Sparger, Jeffrey Roberts, Peter A. Barry, Dennis J. Hartigan-O'Connor, Satya Dandekar

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Subclinical viral infections (SVI), including cytomegalovirus (CMV), are highly prevalent in humans, resulting in lifelong persistence. However, the impact of SVI on the interplay between the host immunity and gut microbiota in the context of environmental exposures is not well defined. We utilized the preclinical nonhuman primate (NHP) model consisting of SVI-free (specific-pathogen-free [SPF]) rhesus macaques and compared them to the animals with SVI (non-SPF) acquired through natural exposure and investigated the impact of SVI on immune cell distribution and function, as well as on gut microbiota. These changes were examined in animals housed in the outdoor environment compared to the controlled indoor environment. We report that SVI are associated with altered immune cell subsets and gut microbiota composition in animals housed in the outdoor environment. Non-SPF animals harbored a higher proportion of potential butyrate-producing Firmicutes and higher numbers of lymphocytes, effector T cells, and cytokine-producing T cells. Surprisingly, these differences diminished following their transfer to the controlled indoor environment, suggesting that non-SPFs had increased responsiveness to environmental exposures. An experimental infection of indoor SPF animals with CMV resulted in an increased abundance of butyrate-producing bacteria, validating that CMV enhanced colonization of butyrate-producing commensals. Finally, non-SPF animals displayed lower antibody responses to influenza vaccination compared to SPF animals. Our data show that subclinical CMV infection heightens host immunity and gut microbiota changes in response to environmental exposures. This may contribute to the heterogeneity in host immune response to vaccines and environmental stimuli at the population level.

Original languageEnglish (US)
Article numbere00167-18
JournalJournal of Virology
Volume92
Issue number13
DOIs
StatePublished - Jul 1 2018

Keywords

  • CMV
  • Cytomegalovirus
  • Gut microbiota
  • Immunity

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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