Core Viewpoint - The article discusses the significant health threats posed by microplastics, particularly polystyrene microplastics (PS-MP), which disrupt macrophage functions and impair the body's ability to clear apoptotic cells, potentially leading to various health issues [3][4][11]. Group 1: Microplastics and Human Health - Microplastics are pervasive in the environment, found in air, water, soil, food, and beverages, leading to widespread human exposure [6][7]. - The World Health Organization estimates that Americans ingest approximately 5 grams of microplastics daily, with concentrations in blood ranging from 1.84 to 4.65 micrograms per milliliter [6][7]. - Microplastics have been detected in various human organs, including blood, liver, lungs, testicles, spleen, brain, placenta, kidneys, and breast milk [6][7]. Group 2: Impact on Macrophage Function - Exposure to PS-MP directly disrupts the efferocytosis process in macrophages, negatively affecting the function and health of multiple organs, including the lungs, liver, and testicles [4][8]. - The study indicates that PS-MP exposure inhibits the ability of macrophages to internalize and digest apoptotic cells, leading to impaired immune responses [8][12]. - Macrophages loaded with PS-MP show defects in phagocytosis, affecting their ability to clear pathogens such as bacteria and fungi [8][12]. Group 3: Mechanisms of Disruption - The accumulation of methylglyoxal (MGO) in PS-MP-loaded macrophages disrupts metabolic and phagocytic processes, leading to altered protein functions due to glycation [9][12]. - The study identifies that the expression of glucose-6-phosphate dehydrogenase (G6PD) is modified in PS-MP-loaded macrophages, which is crucial for the proper digestion of apoptotic cells [9][12]. - Overexpression of the MGO detoxifying enzyme glyoxalase-1 (Glo1) can rescue the efferocytosis defects induced by PS-MP exposure [9][12].

Core Viewpoint - The study reveals that maternal immune activation due to viral infection leads to abnormal secretion of extracellular granzyme B (GzmB) by natural killer (NK) cells, which crosses the maternal-fetal barrier, resulting in the accumulation of fetal macrophages and activation of microglia, ultimately causing neurodevelopmental disorders and behavioral defects in offspring [2][3][6]. Group 1: Research Findings - Maternal NK cells activated by viral infection promote the accumulation of activated macrophages in the fetal brain, leading to neurodevelopmental disorders and behavioral defects in offspring [3][6]. - Extracellular granzyme B (GzmB) is released by maternal CD49a+ tissue-resident NK cell subsets under type I interferon stimulation, crossing the maternal-fetal barrier and promoting the accumulation of fetal macrophages expressing interferon-stimulated genes (ISG) and activation of microglia [3][6]. - Targeting extracellular GzmB by systemic administration of serine protease inhibitor Serpina3n or knocking out the GzmB gene in maternal NK cells can alleviate neuroimmune disorders in the fetal brain induced by maternal immune activation [3][6]. Group 2: Implications - The findings indicate that exposure to a disrupted maternal environment reprograms the immune function of decidual NK cells, disrupting the neuroimmune balance in the fetus and increasing the risk of neurodevelopmental disorders in offspring [6].