The role of primary infection of Schwann cells in the aetiology of infective inflammatory neuropathies.

Numerous different pathogens are responsible for infective peripheral neuropathies and this is generally the result of the indirect effects of pathogen infection, namely anti pathogen antibodies cross reacting with epitopes on peripheral nerve, auto reactive T cells attacking myelin, circulating immune complexes and complement fixation. Primary infection of Schwann cells (SC) associated with peripheral nerve inflammation is rare requiring pathogens to cross the Blood Peripheral Nerve Barrier (BPNB) evade anti-pathogen innate immune pathways and invade the SC. Spirochetes Borrelia bourgdorferi and Trepomema pallidum are highly invasive, express surface lipo proteins, but despite this SC are rarely infected. However, Trypanosoma cruzi (Chaga's disease) and Mycobacterium leprae. Leprosy are two important causes of peripheral nerve infection and both demonstrate primary infection of SC. This is due to two novel strategies; T. cruzi express a trans-silalidase that mimics host neurotrophic factors and infects SC via tyrosine kinase receptors. M. leprae demonstrates multi receptor SC tropism and subsequent infection promotes nuclear reprogramming and dedifferentiation of host SC into progenitor stem like cells (pSLC) that are vulnerable to M. leprae infection. These two novel pathogen evasion strategies, involving stem cells and receptor mimicry, provide potential therapeutic targets relevant to the prevention of peripheral nerve inflammation by inhibiting primary SC infection.

Microbiological diversity associated with the spontaneous wet method of coffee fermentation.

The evaluation of the microbiota present during coffee wet fermentation was done in two distinct regions of Minas Gerais, Brazil: one farm in the South of Minas Gerais (Lavras=L) and another farm in the savannah region (Monte Carmelo=MC). The yeast population ranged from 2.48 to 4.92 log CFU/g and from 2 to 4.81 log CFU/g, the mesophilic bacteria population ranged from 3.83 to 8.47 log CFU/g and from 5.37 to 7.36 log CFU/g, and the LAB population ranged from 2.57 to 5.66 log CFU/g and from 3.40 to 4.49 log CFU/g in the L and MC farms, respectively. Meyerozyma caribbica and Hanseniaspora uvarum were the dominant yeasts in coffee wet fermentation at L farm, and Torulaspora delbrueckii was the dominant yeast at MC farm. The species Staphylococcus warneri and Erwinia persicina were the predominant bacteria at L farm, and Enterobacter asburiae and Leuconostoc mesenteroides were the dominant species at MC farm. Lactic acid was the principal acid detected, reaching 2.33 g/kg at L farm and 1.40 g/kg at MC farm by the end of the process. The volatiles composition was similar for roasted coffee from the two different regions and furans, acids, and alcohol were the main groups detected. Temporal Dominance Sensation (TDS) analyses showed that the coffee beverage from L farm was dominated by citrus and herbaceous sensory characteristics, while the coffee from MC farm was dominated by citrus, herbaceous, and nuts sensory characteristics. Evaluating the microbiota in these two regions was important in improving the knowledge of the microbial species present during coffee wet fermentation in Brazil.

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.

Reprogramming adult Schwann cells to stem cell-like cells by leprosy bacilli promotes dissemination of infection.

Differentiated cells possess a remarkable genomic plasticity that can be manipulated to reverse or change developmental commitments. Here, we show that the leprosy bacterium hijacks this property to reprogram adult Schwann cells, its preferred host niche, to a stage of progenitor/stem-like cells (pSLC) of mesenchymal trait by downregulating Schwann cell lineage/differentiation-associated genes and upregulating genes mostly of mesoderm development. Reprogramming accompanies epigenetic changes and renders infected cells highly plastic, migratory, and immunomodulatory. We provide evidence that acquisition of these properties by pSLC promotes bacterial spread by two distinct mechanisms: direct differentiation to mesenchymal tissues, including skeletal and smooth muscles, and formation of granuloma-like structures and subsequent release of bacteria-laden macrophages. These findings support a model of host cell reprogramming in which a bacterial pathogen uses the plasticity of its cellular niche for promoting dissemination of infection and provide an unexpected link between cellular reprogramming and host-pathogen interaction.

Oblique radial glial divisions in the developing mouse neocortex induce self-renewing progenitors outside the germinal zone that resemble primate outer subventricular zone progenitors.

Radial glia cells function as neural stem cells in the developing brain and generate self-renewing and differentiating daughter cells by asymmetric cell divisions. During these divisions, the apical process or basal process of the elongated epithelial structure is asymmetrically partitioned into daughter cells, depending on developmental contexts. However, in mammalian neurogenesis, the relationship between these subcellular structures and self-renewability is largely unknown. We induced oblique cleavages of radial glia cells to split the apical and basal processes into two daughters, and investigated the fate and morphology of the daughters in slice cultures. We observed that the more basal daughter cell that inherits the basal process self-renews outside of the ventricular zone (VZ), while the more apical daughter cell differentiates. These self-renewing progenitors, termed "outer VZ progenitors," retain the basal but not the apical process, as recently reported for the outer subventricular zone (OSVZ) progenitors in primates (Fietz et al., 2010; Hansen et al., 2010); to self-renew, they require clonal Notch signaling between sibling cells. We also found a small endogenous population of outer VZ progenitors in the mouse embryonic neocortex, consistent with a low frequency of oblique radial glia divisions. Our results describe the general role of the basal process in the self-renewal of neural progenitors and implicate the loss of the apical junctions during oblique divisions as a possible mechanism for generating OSVZ progenitors. We propose that mouse outer VZ progenitors, induced by oblique cleavages, provide a model to study both progenitor self-renewal and OSVZ progenitors.

Integrin beta 4 in neural cells.

Integrin beta 4, one of the heterodimeric receptors, is expressed predominantly on epithelial cells. It is concentrated at the basement membrane zone, where it localizes to specialized adhesion structures called hemidesmosomes. In addition to its adhesive functions, novel insights have emerged regarding the specific roles of integrin beta 4 in their attachment to extracellular matrix and in their signal transduction pathways within the central nervous system (CNS) and peripheral nervous system in the past few years. It has been reported that integrin beta 4 is expressed in several kinds of neural cells including astrocyte, Schwann cells, neurons, and neural stem cells. In the mean while, it is expressed by some Schwann cells in the peripheral nervous system and mediated the Mycobacterium leprae invade the peripheral nervous system to reach the Schwann cells. This review highlights recent progress in the function and regulation of integrin beta 4 in neural cells.

[In vitro induction of differentiation from embryonic stem cells: looking forward to regenerative medicine].

Embryonic stem (ES) cells are pluripotential cells, and enable us to study mechanisms of cell differentiation. Gene disruption of ES cells by homologous recombination is to be clear the function of targeted genes. Recently, it has been reported that bone marrow hematopoietic stem cells have a potential to differentiate into neuronal cell, muscle cell, liver cell, epidermal cell, and also epithelial cell lineages. Moreover, cloned animals from somatic cell nuclei were produced. Here, we show osteoclastogenesis, and endothelial cell-genesis from single ES cell, and discuss the possibility for organogenesis in vitro. Furthermore, we would like to summon to understand usefulness and dangerousness of the regenerative medicine.

The generation of antigen-specific, major histocompatibility complex-restricted cytotoxic T lymphocytes of the CD4+ phenotype. Enhancement by the cutaneous administration of interleukin 2.

We have examined an in vitro system in which PBMC from purified protein derivative (PPD)-sensitized patients generate CTL after in vitro activation with antigen. These cells selectively destroy mycobacterial antigen PPD-pulsed monocyte targets. These CTL are of the CD4+ phenotype and exhibit MHC class II restriction. After exposure to antigen these cells require 5-7 d for maximal development, whereas, a separate antigen-independent population is generated within 3-4 d. CD8+ cells are poorly, if not at all, cytotoxic under similar conditions. Cells with properties of the NK and LAK lineage are also present in these cultures and kill other specific targets. Human rIL-2 was injected into the skin of lepromatous patients at 10-micrograms doses, given at 48-h intervals, for three doses. Peripheral blood cells obtained 8-14 d after the initiation of IL-2 injection demonstrated enhanced antigen-dependent destruction of monocyte targets. The efficacy of antigen-dependent and -independent populations and their amplification by IL-2-dependent mechanisms is discussed in terms of the local destruction of parasitized macrophages and the subsequent disposal of M. leprae.