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Pathogenicity and Virulence
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
A phagosome formed through a conventional process of phagocytosis undergoes sequential steps of maturation which culminate in fusion with surrounding lysosomes to form a phagolysosome. Early phagosomes contain products of the oxidative burst and have a pH close to 6, allowing optimal function of the highly bactericidal cationic peptides (defensins) and cationic proteins. At later stages the pH drops to less than 5.5, forming acid conditions ideal for the function of lysosomal enzymes. Lysosomal constituents begin to be transferred across cell membranes of late phagosomes and attain their highest concentrations upon formation of the phagolysosome.
Macrophages As Effectors Of Cell-Mediated Immunity
Published in Hans H. Gadebusch, Phagocytes and Cellular Immunity, 2020
Leake et al.322 made electron microscopic observations within rabbit alveolar macrophages on the breakdown of several bacteria (Listeria monocytogenes, Salmonella typhi, and Staphylococcus aureus). Both normal macrophages and macrophages from rabbits with BCG-induced pulmonary granulomas were studied. As with Af. smegmatis, there was no fusion of large electron-dense, lysosome-like bodies with the phagosomes in the granulomatous macrophages, but in both types of cells there was fusion of smaller vesicles with the phagosomes. Nevertheless, the bacteria rapidly showed signs of damage. There was often a breakdown of the membrane of the phagosome. Around the phagosome there was often a change in the cell cytoplasm with the appearance of nonmembrane-bound granular or fibrillar dense material; such material was sometimes seen within the phagosome.
Inflammation
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Ingestion and phagosome formation is an energy-dependent process and requires Ca2+ and Mg2+, while the role of cyclic AMP is questioned.394 Phagocytes extend pseudopodia around the attached particles; these then become fused and encased in a phagocytotic vacuole or phagosome. The phagosome moves away from the cell membrane and further fuses with cytoplasmic granules.441 The migrating pseudopodia contain a rich network of microfilaments containing actin and myosin which interact with microtubules during ingestion.
Mechanisms of cellular and humoral immunity through the lens of VLP-based vaccines
Published in Expert Review of Vaccines, 2022
Hunter McFall-Boegeman, Xuefei Huang
Because most VLP-based vaccines targeting T cell responses do not attempt to directly activate T cells, attention must be paid to the cross-presentation pathway in APCs. Cross-presentation is not as simple as the name suggests. It is not a single pathway but is a combination of multiple pathways that result in the same outcome, that is, fragments of proteins of extracellular origin presented on MHC class I molecules. Figure 2 shows the complex nature of cross-presentation. The first step regardless of pathway is phagocytosis of the VLP by the APC. The phagosome then fuses with the lysosome creating a phagolysosome. Here is where the pathways diverge. There are three main cross-presentation pathways with each having minor pathways, which are still being fiercely debated in the literature[112,114–116].
Lipid droplets diversity and functions in inflammation and immune response
Published in Expert Review of Proteomics, 2021
Filipe S. Pereira-Dutra, Patrícia T. Bozza
During the parasite and bacterial infections, LDs are redistributed or recruited to the vicinity of pathogen-containing phagosome through mechanisms that involve complex pathogen- and host-derived signaling [119,213,214]. Physical interactions between LDs and phagosomes has been demonstrated, enabling bidirectional content exchange between LDs and phagosomes containing pathogens [100,118,215–217]. In Mycobacterium bovis infection, the late endosome protein Rab7 and its protein effector Rab-interacting lysosomal protein (RILP) were shown essential to the interaction between LD and M. bovis containing-phagosomes and also involves pathogen-derived cell wall molecules including lipoarabinomannan and PIM [165]. In turn, the capture and translocation of LD into the chlamydial inclusion have been associated with chlamydial protein Lda3 [218], probably forming a tethering structure between LDs and the inclusion membrane. Altogether, LD-phagosome interactions are controlled pathogen components, which enables the exchange of contents between LDs and phagosomes, and may represent a fundamental aspect of bacterial pathogenesis and immune evasion
Role of macrophage in nanomedicine-based disease treatment
Published in Drug Delivery, 2021
Siwei Song, Hui Xia, Mengfei Guo, Sufei Wang, Shujing Zhang, Pei Ma, Yang Jin
Cellular uptake of nanomedicines is generally through phagocytosis (particles larger than 0.5 μm) and pinocytosis (uptake of fluids and solutes) (Patel et al., 2019). Phagocytosis is restricted to specialized phagocytic cells such as macrophages, neutrophils, monocytes, and dendritic cells. The phagocytic process begins with particle recognition and binding with receptors on the surface of the host cell, leading to the engulfment of particles into the cell and subsequent formation of phagosomes. Through a series of physical processes, the particle is transferred to late phagosomes and ultimately lysosomes, forming a phagolysosome (Sahay et al., 2010) (see Figure 2(A)). The physicochemical properties of nanomedicines often determine the efficiency of phagocytosis and the targeting effect of macrophages to the particles; these include shape, size, surface charge, suitable ligands, and so on. Table 1 lists several factors that affect the absorption of nanomedicines by macrophages.