Patterns, Receptors, and Signals: Regulation of Phagosome Maturation

Abstract

Recognition of microbial pathogens and dead cells and their phagocytic uptake by specialized immune cells are essential to maintain host homeostasis. Phagosomes undergo fusion and fission events with endosomal and lysosomal compartments, a process called 'phagosome maturation', which leads to the degradation of the phagosomal content. However, many phagocytic cells also act as antigen-presenting cells and must balance degradation and peptide preservation. Emerging evidence indicates that receptor engagement by phagosomal cargo, as well as inflammatory mediators and cellular activation affect many aspects of phagosome maturation. Unsurprisingly, pathogens have developed strategies to hijack this machinery, thereby interfering with host immunity. Here, we highlight progress in this field, summarize findings on the impact of immune signals, and discuss consequences for pathogen elimination.

Keywords: antigen presentation; host–pathogen interaction; immune response; inflammation; phagocytosis; phagosome maturation.

Figure I

Title.

Figure 1

Key Figure: Impact of Immune Signals on Phagosome Maturation in Dendritic Cells (DCs) and Macrophages (MΦs) Different immune signals, which are either present at the phagocytic particle or sensed in the phagocyte environment, can have different impacts on phagosome maturation. The influence of these immune signals is shown for DCs (A) and MΦs (B), together with their respective receptors. Signal sensing labeled in yellow demonstrates an induction and/or acceleration of phagosome maturation, while signal sensing in blue symbolizes delayed phagosome maturation kinetics. For receptors shown in gray associated with the phagosome, no direct influence on phagosome maturation kinetics has yet been demonstrated, although some have an impact on other phagocyte functions, such as the induction of proinflammatory cytokine production. Abbreviations: EE, early endosome; IFN, interferon; IL, interleukin; LE, late endosome; LPS, lipopolysaccharide; LYS, lysosome; Pam3, Pam3CSK4; polyU, polyuridylic acid; TLR, Toll-like receptor; Zym., zymosan (see Glossary for detailed explanations).

Figure 2

Strategies of Pathogens to Interfere with Phagosome Maturation and Host Immunity.. In this scheme, the major features that Legionella pneumophila (A) and Mycobacterium tuberculosis (B) have developed to evade host cell immunity are summarized. Their impact on phagosome maturation and other phagocyte functions is indicated. Abbreviations: EE, early endosome; ER, endoplasmic reticulum; LCV, L. pneumophila-containing vacuole; LE, late endosome; LYS, lysosome; MCV, Mycobacterium tuberculosis-containing vacuole; MITO, mitochondrion; NUC, nucleus.