Phagocytes in Immunity: Linking Material Internalization to Immune Responses and Therapeutic Strategies

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Background

Phagocytes, including neutrophils, macrophages, and dendritic cells, are key to the maintenance of immunity in metazoans. They are essential to both the direct clearance of invading pathogens as well as to the initiation of adaptive immune responses. A distinctive characteristic of phagocytes is their ability to survey tissues and respond to potential threats by internalizing and processing large quantities of exogenous material through the process of phagocytosis. Phagocytes possess a range of phagocytic receptors that can signal for large-scale cytoskeletal remodeling and the ultimate internalization of large particulate structures, such as invading microbes or homeostatic debris. Simultaneously, phagocytes engulf comparatively large quantities of extracellular fluid through the closely related process of macropinocytosis.

Phagocytic and macropinocytic cargo is processed in specialized organelles known as phagosomes and macropinosomes. The unique environment within these compartments allows for the killing of microbial threats, the extraction of antigen for presentation to cells of the adaptive immune system, and the delivery of microbe-associated molecular patterns (MAMPs) to intracellular pattern recognition receptors (PRRs).

Both phagocytosis and macropinocytosis are tuneable processes. Exposure of phagocytes to context-specific environmental cues results in the large-scale restructuring of the phagocytic machinery. For example, macrophage subsets polarized with distinct stimuli express different arrays of phagocytic receptors and as a result internalize distinct phagocytic targets. Beyond uptake, polarized macrophages also change the way they process phagosomal cargo. Similarly, macropinocytic activity is dependent on the polarizing stimulus. This allows for the context-specific, and appropriate, handling of distinct targets favoring either the rapid removal of metabolic debris or the killing and extraction of antigen from microbial cargo.

Additionally, phagocytosis and macropinocytosis are increasingly recognized as a key step in the immune response to “altered self” disorders. The direct clearance of malignant tumor cells by macrophages and the presentation of cell-associated antigen by dendritic cells to T cells have both emerged as areas of intense study in cancer research.

The focus of this Research Topic will be to highlight the basic mechanisms by which phagocytes contribute to the maintenance of homeostasis, innate immunity, inflammation, and the onset of adaptive immunity. Emphasis will be placed on the cell biology of phagocyte-specific functions including, but not limited to, (i) the related processes of phagocytosis and macropinocytosis, (ii) how these processes contribute to the immune and homeostatic functions of phagocytes and (iii) the emerging immunotherapeutic strategies that target phagocyte function.

The submission of Original Research, Review, Mini Review, and Perspective articles that cover, but are not limited to, the following subtopics will be encouraged:

1. Mechanisms of macropinocytic and phagocytic pathways in different phagocytes
2. Phagosomal maturation and cargo processing
3. Mechanisms of phagosome trafficking, repair, and resolution
4. Connections between phagocytosis/macropinocytosis and PRRs
5. Phagocytosis in tissue development remodeling
6. Effect of polarization on phagocytosis and cargo handling
7. Phagocytosis/macropinocytosis and antigen presentation
8. Phagocytosis checkpoints in immunotherapy
9. New technologies to study phagocytosis and macropinocytosis

Keywords: phagocyte, macrophage, dendritic cell, neutrophil, microglia, phagocytosis, macropinocytosis, antigen presentation, inflammation, phagocytic receptors, innate immunity

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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