ER‐mediated phagocytosis: myth or reality?

Dear Editor, In a manuscript by Touret et al. [1], published in the present issue, the authors oppose a so-called " conventional model " of phagocytosis involving the plasma membrane (PM) and early endosomes to an " endoplasmic reticulum (ER)-mediated " model, where the ER is the sole source of initial membrane for the formation of phagosomes. We argue that none of these models integrate accurately the sum of knowledge acquired in the last few years on membrane trafficking events during phagocytosis. Moreover, the ER-mediated model shown certainly does not represent our current view. It would have been more appropriate to present as a conventional model the original concept derived from Elie Metchnikoff's observations, where the PM is the sole source of membrane, and the alternative view is that other organelles, including various endo-cytic organelles and ER, also contribute membrane, as proposed recently [2]. Indeed, the seminal work of Metchnikoff at the end of the 19th century led to the proposal that phagosomes were formed by the invagination of the PM. For over a century, this prevailing view was unchallenged. However, it appeared to many scientists that the use of the cell surface might waste an important membrane to form a compartment destined for degradation and that in some conditions, the membrane needed to form phagosomes was exceeding the actual cell surface, implying that membranes from endovacuolar organelles might participate directly in the formation of phagosomes. It is only in the last few years that evidence for the contribution of several organelles in the formation of phagosomes at the cell surface, including recycling and late endosomes, was provided in the Touret et al. [1] paper. More recently, we and others [3, 4] presented a significant body of evidence indicating that ER is also directly involved in the formation of nascent phagosomes. Although the functional advantage of using recycling or early endosome membranes for the formation of phagosomes is still unclear, the contribution of ER led to the proposal that ER-mediated phagocytosis must confer functional properties, enabling phagosomes to play a direct role in the processing and presentation of exogenous peptides on major histocompatibility complex class I molecules , a process referred to as cross-presentation [2]. Following this proposal, three independent studies published simultaneously confirmed that phagosomes, in macrophages and den-dritic cells, were competent organelles for cross-presentation [5–7]. In the Touret et al. [1] manuscript, the authors challenge the idea that …