The immunostimulatory activity of sea spray aerosols: bacteria and endotoxins activate TLR4, TLR2/6, NF-κB and IRF in human cells

Frequent exposure to sea spray aerosols (SSA) containing marine microorganisms and bioactive compounds may influence human health. However, little is known about potential immunostimulation by SSA exposure. This study focuses on the effects of marine bacteria and endotoxins in SSA on several receptors and transcription factors known to play a key role in the human innate immune system. SSA samples were collected in the field (Ostend, Belgium) or generated in the lab using a marine aerosol reference tank (MART). Samples were characterized by their sodium contents, total bacterial counts, and endotoxin concentrations. Human reporter cells were exposed to SSA to investigate the activation of toll -like receptor 4 (TLR4) in HEK-Blue hTLR4 cells and TLR2/6 in HEK-Blue hTLR2/6 cells, as well as the activation of nuclear factor kappa B (NF- kappa B) and interferon regulatory factors (IRF) in THP1-Dual monocytes. These responses were then correlated to the total bacterial counts and endotoxin concentrations to explore dose -effect relationships. Field SSA contained from 3.0 x 10 3 to 6.0 x 10 5 bacteria/m 3 air (averaging 2.0 +/- 1.9 x 10 5 bacteria/m 3 air) and an endotoxin concentration ranging from 7 to 1217 EU/m 3 air (averaging 389 +/- 434 EU/m 3 air). In contrast, MART SSA exhibited elevated levels of total bacterial count (from 2.0 x 10 5 to 2.4 x 10 6 , averaging 7.3 +/- 5.5 x 10 5 cells/m 3 air) and endotoxin concentration from 536 to 2191 (averaging 1310 +/- 513 EU/m 3 air). SSA samples differentially activated TLR4, TLR2/6, NF -KB and IRF. These immune responses correlated dose -dependently with the total bacterial counts, endotoxin levels, or both. This study sheds light on the immunostimulatory potential of SSA and its underlying mechanisms, highlighting the need for further research to deepen our understanding of the health implications of SSA exposure.