RT Journal Article
SR Electronic
T1 Humoral immune response to adenovirus induce tolerogenic bystander dendritic cells that promote generation of regulatory T cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 334508
DO 10.1101/334508
A1 Thi Thu Phuong Tran
A1 Karsten Eichholz
A1 Patrizia Amelio
A1 Crystal Moyer
A1 Glen R Nemerow
A1 Matthieu Perreau
A1 Franck JD Mennechet
A1 Eric J Kremer
YR 2018
UL http://biorxiv.org/content/early/2018/05/30/334508.abstract
AB Following repeated encounters with adenoviruses most of us develop robust humoral and cellular immune responses that are thought to act together to combat ongoing and subsequent infections. Yet in spite of robust immune responses, adenoviruses establish subclinical persistent infections that can last for decades. While adenovirus persistence pose minimal risk in B-cell compromised individuals, if T-cell immunity is severely compromised, reactivation of latent adenoviruses can be life threatening. This dichotomy led us to ask how anti-adenovirus antibodies influence adenovirus-specific T-cell immunity. Using primary human blood cells, transcriptome and secretome profiling, and pharmacological, biochemical, genetic, molecular, and cell biological approaches, we initially found that healthy adults harbor adenovirus-specific regulatory T cells (Tregs). As peripherally induced Tregs are generated by tolerogenic dendritic cells (DCs), we then addressed how tolerogenic DCs could be created. Here, we demonstrate that DCs that take up immunoglobulin-complexed (IC)-adenoviruses create an environment that causes bystander DCs to become tolerogenic. These adenovirus antigen-loaded tolerogenic DCs can drive naïve T cells to mature into adenovirus-specific Tregs. Our results may provide ways to improve antiviral therapy and/or pre-screening high-risk individuals undergoing immunosuppression.Author summary While numerous studies have addressed the cellular and humoral response to primary virus encounters, relatively little is known about the interplay between persistent infections, neutralizing antibodies, antigen-presenting cells, and the T-cell response. Our studies suggests that if adenovirus–antibody complexes are taken up by professional antigen-presenting cells (dendritic cells), the DCs generate an environment that causes bystander dendritic cells to become tolerogenic. These tolerogenic dendritic cells favors the creation of adenovirus-specific regulatory T cells. While this pathway likely favors pathogen survival, there may be advantages for the host also.