Progress of phagosome maturation and function in neutrophil, macrophage and dendritic cell / 中华微生物学和免疫学杂志

Phagosomes undergo the fusion of early endosomes, late endosomes and lysosomes, and then degrade antigens and kill pathogenic microorganisms, which is called phagosome maturation. The functional differences of phagosomes after maturation in different immune cells lead to distinct characteristics on their processing of phagocytic antigens. It has been found that the antigen degradation ability of immune cells is opposite to their antigen presentation capacity through comparing the functional differences of phagosomes from neutrophils, macrophages and dendritic cells after antigens uptake. Among them, dendritic cells have the strongest antigen presentation capacity, followed by macrophages and neutrophils. The in-depth study of immune cell phagosome maturation and antigen presentation will provide new strategies for vaccine development and immunotherapy.

Modulation of phagolysosome maturation by bacterial tlyA gene product.

The pathogenic traits of TlyA proteins of Mycobacterium tuberculosis are not known. Expressions of TlyA in bacteria that do not express endogenous TlyA adhere better to RAW264.7 macrophages and get phagocytosed efficiently. The internalized bacteria avoid acidification to the extent of >65% in the case of both TlyA-expressing E. coli and M. smegmatis. Consistent with this observation, we have observed decreased co-localizaton of Lysosomal Membrane Associated Protein-1 (~35%), Early Endosomal Antigen-1 (~34%), Rab5 (~30%) and Rab7 (~35%) and enhanced colocalizaton of Rab14 (~80%) on both TlyA-expressing bacteria as well as on TlyA-coated latex beads. These results suggest that the mycobacterial TlyA, in general, can modulate phagolysosome maturation pathway immediately after entry into macrophages, while other important molecules may aid the bacterium for long-term, intracellular survival at later point of time.

Actin-interacting and flagellar proteins in Leishmania spp: bioinformatics predictions to functional assignments in phagosome formation

Several motile processes are responsible for the movement of proteins into and within the flagellar membrane, but little is known about the process by which specific proteins (either actin-associated or not) are targeted to protozoan flagellar membranes. Actin is a major cytoskeleton protein, while polymerization and depolymerization of parasite actin and actin-interacting proteins (AIPs) during both processes of motility and host cell entry might be key events for successful infection. For a better understanding the eukaryotic flagellar dynamics, we have surveyed genomes, transcriptomes and proteomes of pathogenic Leishmania spp. to identify pertinent genes/proteins and to build in silico models to properly address their putative roles in trypanosomatid virulence. In a search for AIPs involved in flagellar activities, we applied computational biology and proteomic tools to infer from the biological meaning of coronins and Arp2/3, two important elements in phagosome formation after parasite phagocytosis by macrophages. Results presented here provide the first report of Leishmania coronin and Arp2/3 as flagellar proteins that also might be involved in phagosome formation through actin polymerization within the flagellar environment. This is an issue worthy of further in vitro examination that remains now as a direct, positive bioinformatics-derived inference to be presented.

A Case of Congenital Self-Healing Reticulohistiocytosis

Congenital self-healing reticulohistiocytosis (CSHRH) is a rare Langerhans cell disorder usually showing spontaneous resolution within 3-4 months. By electron microscopy, the identification of Birbeck granules and laminated dense bodies in the infiltrated cells is mandatory for the diagnosis of CSHRH. However, in some reported cases, Birbeck granules could not be demonstrated and only cytoplasmic dense bodies were seen. If the lesion is more advanced, Birbeck granules are transformed to lysosomes, i.e., 'unique phagosomes', in which they are degraded. A 2-month-old Korean girl presented with congenital, numerous red-brown pigmented papules on the left side of trunk and upper extremity without systemic symptoms. A biopsy specimen demonstrated papillary dermis containing epidermotropic infiltrates of histiocytes with abundant eosinophilic cytoplasm. Some had kidney-shaped nuclei and PAS-positive cytoplasmic inclusions. Immunohistochemically, infiltrating cells expressed S-100 protein and ultrastructurally, no Birbeck granules but many dense laminated bodies and unique phagosomes were found. It was ten months since the skin lesions developed that they have started resolving.

Degradation of phagosomes and diurnal changes of lysosomes in rabbit retinal pigment epithelium

Diurnal changes of lysosomes including ultrastructural changes of phagosomes and acid phosphatase reactions in phagosomes, as well as diurnal biochemical changes in cathepsin D activity, were studied in the retinal pigment epithelium (RPE) of the rabbit. The rabbit was maintained on a natural light-dark cycle over seven days in fall and was sacrificed at various times during the day and night. The number of lysosomes or phagosomes in the RPE was the highest at 1.5 hours after exposure to sunlight (8:00 AM), and thereafter decreased with time. Three types of phagosomes were observed and acid phosphatase reactions were different in each type of phagosome; the fresh phagosomes were negative or positive, lamellar bodies positive, and dense bodies partially positive. The biochemical activity of cathepsin D was the highest at 8:00 AM, and this was consistent with the time of peak in phagocytic activity in the RPE. This report shows that phagocytic activity in the RPE occurred in the early stage after exposure to sunlight, and that fresh phagosomes were sequentially degraded to lamellar or dense bodies. Cathepsin D activity also increased, and this was consistent with the phagocytic activity in the RPE.

Lysosomal Changes of Retinal Pigment Epithelium

This study was carried out to investigate diurnal changes of lysosomes includ ing ultrastructural changes of phagosomes and activity of acid phosphatase in the phagosomes and diurnal biochemical changes of cathepsin D activity of rab bits. The eyes were obtained at 0:00, 4:00, 8:00, 12:00, 16:00 and 20:00 o'clock. The number of lysosomes and phagosomes in retinal pigment epithelium(RPE) was the highest at 8:00 o'clock, thereafter decreased with time. There were three types of phagosomes; fresh phagosomes showed both negative and positive reactions, lamellar bodies positive, and dense bodies partially positive. The biochemical activity of cathepsin D was the highest at 8:00 o'clock consistent with the time of peak in phagocytic activities of RPE. According to the above results, it would be suggested that the maximum shedding of outer segments and phagocytic activity of RPE occurred on the early stage after sunlight exposure, and that the phagosomes were degraded to the lamellar bodies and dense bodies sequentially. And also activity of the cathepsin D would be increased consistent with the phagocytic activity of RPE.