Bacterial-induced cell reprogramming to stem cell-like cells: new premise in host-pathogen interactions.

Bacterial pathogens employ a myriad of strategies to alter host tissue cell functions for bacterial advantage during infection. Recent advances revealed a fusion of infection biology with stem cell biology by demonstrating developmental reprogramming of lineage committed host glial cells to progenitor/stem cell-like cells by an intracellular bacterial pathogen Mycobacterium leprae. Acquisition of migratory and immunomodulatory properties of such reprogrammed cells provides an added advantage for promoting bacterial spread. This presents a previously unseen sophistication of cell manipulation by hijacking the genomic plasticity of host cells by a human bacterial pathogen. The rationale for such extreme fate conversion of host cells may be directly linked to the exceedingly passive obligate life style of M. leprae with a degraded genome and host cell dependence for both bacterial survival and dissemination, particularly the use of host-derived stem cell-like cells as a vehicle for spreading infection without being detected by immune cells. Thus, this unexpected link between cell reprogramming and infection opens up a new premise in host-pathogen interactions. Furthermore, such bacterial ingenuity could also be harnessed for developing natural ways of reprogramming host cells for repairing damaged tissues from infection, injury and diseases.

Abilities of human oligodendroglial cells and mouse Schwann cells to phagocytose Mycobacterium leprae and other mycobacteria.

Human oligodendroglial KG-1-C cells derived from human cerebral mixed glioma and mouse Schwann cells derived from dorsal root ganglion were studied with respect to their abilities to phagocytose various mycobacteria, especially Mycobacterium leprae, and other microorganisms. KG-1-C cells phagocytosed M. leprae at a markedly higher rate than BALB/3T3, BHK 21, HeLa S3, mKS-A TU-7, XC, TSV-5, N-18, and Schwann cells but at a lower rate than peritoneal macrophages. Schwann cells also exhibited substantial phagocytic ability against M. leprae, and their phagocytic rate against M. leprae was much higher than that of N-18 cells, derived from neurons. KG-1-C and Schwann cells phagocytosed mycobacteria other than M. leprae, and their phagocytic patterns with various mycobacteria were similar, thereby suggesting that their abilities to phagocytose mycobacteria were based on the same cellular mechanism. The time course of phagocytosis of M. leprae by KG-1-C cells markedly differed from that by macrophages, indicating differences in the cellular mechanisms of M. leprae phagocytosis. KG-1-C cells also ingested microorganisms other than acid-fast bacilli, such as Staphylococcus aureus, Listeria monocytogenes, Bacillus subtilis, and Escherichia coli but not Candida albicans. They also phagocytosed latex beads (0.8-micron diameter) but not sheep erythrocytes. Microscopically, most mycobacterial cells were ingested in the perikaryon of KG-1-C cells and Schwann cells.

Mechanisms of phagocytosis of Mycobacterium leprae and other mycobacteria by human oligodendroglial cells.

The mechanisms by which human oligodendroglial cells, KG-1-C cells, phagocytose mycobacteria, especially Mycobacterium leprae, were studied. The ability of glial cells to phagocytose M. leprae was inhibited by azide, dinitrophenol (inhibitors of oxidative phosphorylation), and iodoacetamide but not fluoride (both are inhibitors of glycolysis). Thus, the energy metabolism dependency is somewhat different from that of peritoneal macrophages and polymorphonuclear leukocytes, the phagocytic capacities of which are mainly dependent on glycolysis. Phagocytosis of M. leprae by KG-1-C cells was markedly suppressed by a microfilament inhibitor (cytochalasin B) but not microtubule inhibitors (colchicine and vinblastine), as with macrophages. The phagocytosis of M. leprae by KG-1-C cells was dependent on the lipid and somewhat on the sugar ligands of the organism. Moreover, the phagocytosis of a given mycobacterium by KG-1-C cells correlated well with its hydrophobicity, thus revealing the importance of some lipid moieties on the surface of bacteria in the establishment of rigid binding interaction of bacteria with KG-1-C cells, before the onset of engulfment. Electric charge of a given microorganism did not correlate with its phagocytosis by KG-1-C cells.