E-cigarette use increases susceptibility to bacterial infection by impairment of human neutrophil chemotaxis, phagocytosis, and NET formation

Am J Physiol Cell Physiol. 2020 Jan 1;318(1):C205-C214. doi: 10.1152/ajpcell.00045.2019. Epub 2019 Oct 30.


E-cigarettes are portrayed as safer relative to conventional tobacco. However, burgeoning evidence suggests that E-cigarettes may adversely affect host defenses. However, the precise mechanisms by which E-cigarette vapor alters innate immune cell function have not been fully elucidated. We determined the effects of E-cigarette exposure on the function and responses to infectious challenge of the most abundant innate immune cell, the neutrophil, using isolated human neutrophils and a mouse model of gram-negative infection. Our results revealed that human neutrophils exposed to E-cigarette vapor had 4.2-fold reductions in chemotaxis toward the bacterial cell-well component f-Met-Leu-Phe (P < 0.001). F-actin polarization and membrane fluidity were also adversely affected by E-cigarette vapor exposure. E-cigarette-exposed human neutrophils exhibited a 48% reduction in production of reactive oxygen species (ROS; P < 0.001). Given the central role of ROS in neutrophil extracellular trap (NET) production, NET production was quantified, and E-cigarette vapor exposure was found to reduce NETosis by 3.5-fold (P < 0.01); formulations with and without nicotine containing propylene glycol exhibiting significant suppressive effects. However, noncanonical NETosis was unaffected. In addition, exposure to E-cigarette vapor lowered the rate of phagocytosis of bacterial bioparticles by 47% (P < 0.05). In our physiological mouse model of chronic E-cigarette exposure and sepsis, E-cigarette vapor inhalation led to reduced neutrophil migration in infected spaces and a higher burden of Pseudomonas. These findings provide evidence that E-cigarette use adversely impacts the innate immune system and may place E-cigarette users at higher risk for dysregulated inflammatory responses and invasive bacterial infections.

Keywords: reactive oxygen species; sepsis; chemotaxis; E-cigarette; human neutrophils; neutrophil extracellular trap; Pseudomonas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemotaxis, Leukocyte*
  • Disease Models, Animal
  • Electronic Nicotine Delivery Systems*
  • Extracellular Traps / immunology*
  • Extracellular Traps / metabolism
  • Extracellular Traps / microbiology
  • Female
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate
  • Membrane Fluidity
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Neutrophils / microbiology
  • Phagocytosis*
  • Pseudomonas Infections / immunology*
  • Pseudomonas Infections / metabolism
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / immunology*
  • Pseudomonas aeruginosa / pathogenicity
  • Reactive Oxygen Species / metabolism
  • Risk Assessment
  • Signal Transduction
  • Vaping / adverse effects*
  • Vaping / immunology


  • Reactive Oxygen Species