Staphylococcus aureus-derived extracellular vesicles induce neutrophilic pulmonary inflammation via both Th1 and Th17 cell responses.
BACKGROUND
Recent evidence indicates that Staphylococcus aureus, one of the most important human pathogens, secretes vesicles into the extracellular milieu.


OBJECTIVE
To evaluate whether inhalation of S. aureus-derived extracellular vesicles (EV) is causally related to the pathogenesis of inflammatory pulmonary diseases.


METHODS
Staphylococcus aureus EV were prepared by sequential ultrafiltration and ultracentrifugation. The innate immune response was evaluated in vitro after the application of EV to airway epithelial cells and alveolar macrophages. In vivo innate and adaptive immune responses were evaluated after airway exposure to EV. Adjuvant effects of EV on the development of hypersensitivity to inhaled allergens were also evaluated after airway sensitization with S. aureus EV and ovalbumin (OVA).


RESULTS
Staphylococcus aureus and S. aureus EV were detected in house dust. Alveolar macrophages produced both tumor necrosis α (TNF-α) and interleukin 6 (IL-6) after in vitro stimulation with S. aureus EV, whereas airway epithelial cells produced only IL-6. Repeated airway exposure to S. aureus EV induced both Th1 and Th17 cell responses and neutrophilic pulmonary inflammation, mainly via a Toll-like receptor 2 (TLR2)-dependent mechanism. In terms of adjuvant effects, airway sensitization with S. aureus EV and OVA resulted in neutrophilic pulmonary inflammation after OVA challenge alone. This phenotype was partly reversed by the absence of interferon γ (IFN-γ) or IL-17.


CONCLUSIONS
Staphylococcus aureus EV can induce Th1 and Th17 neutrophilic pulmonary inflammation, mainly in a TLR2-dependent manner. Additionally, S. aureus EV enhance the development of airway hypersensitivity to inhaled allergens.
Department of Life Science, Pohang University of Science and Technology (POSTECH), Pohang.
M-R
MR
Kim
S-W
SW
Hong
E-B
EB
Choi
W-H
WH
Lee
Y-S
YS
Kim
S G
SG
Jeon
M H
MH
Jang
Y S
YS
Gho
Y-K
YK
Kim
D022162:Cytoplasmic Vesicles / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000276:immunology / Q000648:ultrastructure; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*