Per- and polyfluoroalkyl substances (PFAS) alter immune responses from THP-1 human monocytes

Area of Science:

• Environmental Health Sciences
• Immunotoxicology
• Cellular Biology

Background:

• Per- and Polyfluoroalkyl substances (PFAS) are pervasive environmental contaminants.
• Exposure to PFAS is associated with adverse health outcomes, including immune system dysfunction.
• The precise cellular mechanisms by which PFAS affect immune function are not fully understood.

Purpose of the Study:

• To investigate the direct in vitro effects of various PFAS on THP-1 human monocyte function.
• To elucidate how different PFAS compounds differentially modulate immune cell responses.
• To understand the cellular mechanisms underlying PFAS-induced immune alterations.

Main Methods:

• Utilized THP-1 human monocyte cell line for in vitro studies.
• Exposed cells to specific PFAS, including legacy (PFOA, PFOS), byproduct (NBP2), and next-generation (HFPO-DA/"GenX") compounds.
• Assessed changes in immune cell activation, cytokine profiles, and phenotypic markers.

Main Results:

• All tested PFAS activated THP-1 cells and altered immune function.
• PFOS suppressed inflammatory cytokine release.
• NBP2 and PFO4DA induced mixed inflammatory and anti-inflammatory responses.
• PFOA, HFPO-DA/"GenX", and PFMOAA promoted suppressive phenotypes, similar to tumor-associated macrophages.

Conclusions:

• PFAS, even at non-lethal concentrations, directly interfere with immune cell function.
• Different PFAS compounds exert distinct and often contrasting effects on immune responses.
• Findings highlight the complex immunomodulatory potential of PFAS, impacting cytokine profiles and immune activation states.