Exosomes in fetal bovine serum dampen primary macrophage IL-1β response to lipopolysaccharide (LPS) challenge

• Exosomes are nanoparticles released from cells and modulate many physiological processes.
• Fetal bovine serum (FBS) contains immunologically active exosomes.
• Removing bovine exosomes from culture media alters macrophage cytokine responses to LPS.
• FBS exosomes exert an immunosuppressive impact on cells similar to trophoblast exosomes.

This study identifies a previously unknown immunological function of exosomes present in fetal bovine serum (FBS). Exosomes are small (40–100 nm), biologically active nanoparticles released from cells that associate with a variety of proteins and miRNA. Exosomes are present in nearly all biological fluids, including FBS, a common supplement to cell culture media. While there are a growing number of studies examining cellular responses to exosomes, there is no assessment of how FBS exosomes impact cellular responses to immunological challenges. Our results demonstrate that primary macrophages from Fisher 344 rats cultured with lipopolysaccharide (LPS) in the presence of FBS exosomes exhibit a dose-dependent reduction in IL-1β compared to macrophages cultured in medium supplemented with exosome-depleted FBS. The addition of fetal bovine exosomes also reduced macrophage tumor necrosis factor-alpha (TNF-α) and IL-6, but not IL-10, monocyte chemotactic factor-1 (MCP-1), nitric oxide (NO), or lactose dehydrogenase (LDH) response to LPS. The selectivity of exosomal impact on macrophage IL-1β and pro-inflammatory protein responses may implicate the potential role of exosome-inflammasome interactions. These findings suggest that researchers should consider the immunological influence of FBS exosomes, particularly on IL-1β activity, when studying cells in culture.