Tim4, a macrophage receptor for apoptotic cells, binds polystyrene microplastics via aromatic-aromatic interactions

Area of Science:

• Immunology
• Materials Science
• Toxicology

Background:

• Microplastics are environmental contaminants with poorly understood biological interactions.
• Phagocytes, like macrophages, engulf microplastics, but recognition mechanisms and functional impacts remain unclear.
• T cell immunoglobulin mucin 4 (Tim4) is a macrophage receptor crucial for efferocytosis.

Purpose of the Study:

• To investigate the molecular mechanisms by which macrophages recognize microplastics.
• To determine the impact of microplastic-macrophage interactions on immune responses.
• To explore the potential of microplastics to interfere with efferocytosis.

Main Methods:

• Investigated binding of polystyrene (PS) microparticles and multi-walled carbon nanotubes (MWCNTs) to Tim4.
• Utilized genetic deletion of Tim4 in macrophages to assess its role in microplastic engulfment.
• Assessed inflammatory cytokine secretion (IL-1β, TNF-α) and reactive oxygen/nitric oxide production.
• Examined the effect of PS microparticles on Tim4-mediated efferocytosis of apoptotic cells.

Main Results:

• Tim4 binds PS microparticles and MWCNTs via its extracellular aromatic cluster, establishing a novel interaction interface.
• Tim4 mediates the engulfment of both PS microplastics and MWCNTs by macrophages.
• MWCNT engulfment triggers NLRP3-dependent IL-1β secretion, whereas PS microparticles do not induce acute inflammatory responses.
• PS microparticles competitively inhibit Tim4-mediated efferocytosis of apoptotic cells.

Conclusions:

• PS microplastics interact with macrophages through Tim4 but do not elicit acute inflammation.
• PS microplastics perturb efferocytosis, raising concerns for chronic inflammation and autoimmune disease development with prolonged exposure.
• Understanding microplastic-immune cell interfaces is critical for assessing their health risks.