Cigarette smoke-induced extracellular vesicles from dendritic cells alter T-cell activation and HIV replication

Ashley E. Russell, Zhaohao Liao, Mercedes Tkach, Patrick M. Tarwater, Matias Ostrowski, Clotilde Théry, Kenneth W. Witwer

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Despite decreased rates of tobacco smoking in many areas, cigarette smoking remains a major contributor to many health problems. Cigarette smoking can reduce immune system functioning while concurrently increasing inflammation. Dendritic cells in the lung exposed to cigarette smoke become stimulated and go on to activate T-cells. Extracellular vesicles (EVs) are nano-sized particles released by cells. They participate in intercellular communication by transferring functional proteins and nucleic acids to recipient cells and have been implicated in immune responses. For example, they can display MHC-peptide complexes to activate T-cells. In the current study, we sought to understand the role of cigarette smoke extract (CSE) on dendritic cell-derived EVs and their capacity to activate and differentiate T-cells. Primary human dendritic cells (iDCs) were exposed to CSE and EVs were separated and characterized. We exposed autologous primary CD4 + T-cells to iDC-EVs and observed T helper cell populations skewing towards Th1 and Th17 phenotypes. As HIV + individuals are disproportionately likely to be current smokers, we also examined the effects of iDC-EVs on acutely infected T-cells as well as on a cell model of HIV latency (ACH-2). We found that in most cases, iDC-CSE EVs tended to reduce p24 release from the acutely infected primary T-cells, albeit with great variability. We did not observe large effects of iDC-EVs or direct CSE exposure on p24 release from the ACH-2 cell line. Together, these data suggest that iDC-CSE EVs have the capacity to modulate the immune responses, in part by pushing T-cells towards Th1 and Th17 phenotypes.

Original languageEnglish (US)
Pages (from-to)33-43
Number of pages11
JournalToxicology Letters
Volume360
DOIs
StatePublished - May 1 2022

All Science Journal Classification (ASJC) codes

  • Toxicology

Fingerprint

Dive into the research topics of 'Cigarette smoke-induced extracellular vesicles from dendritic cells alter T-cell activation and HIV replication'. Together they form a unique fingerprint.

Cite this