Phagocytosis is an evolutionarily conserved important immunological process in higher organisms, and acts as the first line of defense against invading pathogenic microbial infections. Additionally, this dynamic innate immune response is also critical for clearing apoptotic cells and/or tissues, is responsible for maintaining homeostasis and acts as a systemic regulator of critical physiological processes such as wound healing and tissue regeneration. Over the past two decades, numerous studies have shown that phagocytosis occurs in three spatiotemporally distinct steps, namely formation, maturation and resolution of the phagosome, and that, both the protein and lipid composition change as a function of the aforementioned steps during this immunological process. While significant knowledge is now available on the proteomic content of a phagosome during the different stages of phagocytosis, the lipidome however, remained lesser explored, until the past few years. In this review, we summarize recent efforts towards mapping the physiological roles and functions of three lipid classes, the phosphatidylinositols, cholesterol and sphingolipids during the various stages of phagocytosis, and discuss strategies evolved by microbes to hijack and/or disrupt these lipid pathways to evade the immune system. We conclude this review with some potential avenues that may be pursued towards mapping hitherto unknown lipid pathways during phagocytosis, and how this research might be beneficial in our ongoing battle to overcome pathogenic infections.

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