Reprogramming diminishes retention of Mycobacterium leprae in Schwann cells and elevates bacterial transfer property to fibroblasts

Toshihiro Masaki,Jinrong Qu,Aidan Mcglinchey,Anura Rambukkana,Simon R Tomlinson

doi:10.12688/f1000research.2-198.v2

Abstract

Bacterial pathogens can manipulate or subvert host tissue cells to their advantage at different stages during infection, from initial colonization in primary host niches to dissemination. Recently, we have shown that Mycobacterium leprae (ML), the causative agent of human leprosy, reprogrammed its preferred host niche de-differentiated adult Schwann cells to progenitor/stem cell-like cells (pSLC) which appear to facilitate bacterial spread. Here, we studied how this cell fate change influences bacterial retention and transfer properties of Schwann cells before and after reprogramming.Using primary fibroblasts as bacterial recipient cells, we showed that non-reprogrammed Schwann cells, which preserve all Schwann cell lineage and differentiation markers, possess high bacterial retention capacity when co-cultured with skin fibroblasts; Schwann cells failed to transfer bacteria to fibroblasts at higher numbers even after co-culture for 5 days. In contrast, pSLCs, which are derived from the same Schwann cells but have lost Schwann cell lineage markers due to reprogramming, efficiently transferred bacteria to fibroblasts within 24 hours.ML-induced reprogramming converts lineage-committed Schwann cells with high bacterial retention capacity to a cell type with pSLC stage with effective bacterial transfer properties. We propose that such changes in cellular properties may be associated with the initial intracellular colonization, which requires long-term bacterial retention within Schwann cells, in order to spread the infection to other tissues, which entails efficient bacterial transfer capacity to cells like fibroblasts which are abundant in many tissues, thereby potentially maximizing bacterial dissemination. These data also suggest how pathogens could take advantage of multiple facets of host cell reprogramming according to their needs during infection.

Highlights

The peripheral nervous system (PNS) is the preferred residence for one of the oldest bacterial pathogens known to mankind, Mycobacterium leprae (ML)
We have recently shown that once infected these de-differentiated Schwann cells purified from adult nerves, they undergo a reprogramming process and convert to highly immature progenitor/stem cell-like cells that are more suitable for spreading infection to other tissues either by direct redifferentiation or through macrophages[7]
We determine if ML infection at day 3 changed Schwann cell lineage marker expression when compared with progenitor/stem cell-like cells (pSLC), which are known to be reprogrammed cells exhibiting the loss of Schwann cell lineage markers[7]

Summary

Introduction

The peripheral nervous system (PNS) is the preferred residence for one of the oldest bacterial pathogens known to mankind, Mycobacterium leprae (ML). Conclusions: ML-induced reprogramming converts lineage-committed Schwann cells with high bacterial retention capacity to a cell type with pSLC stage with effective bacterial transfer properties We propose that such changes in cellular properties may be associated with the initial intracellular colonization, which requires long-term bacterial retention within Schwann cells, in order to spread the infection to other tissues, which entails efficient bacterial transfer capacity to cells like fibroblasts which are abundant in many tissues, thereby potentially maximizing bacterial dissemination. These data suggest how pathogens could take advantage of multiple facets of host cell reprogramming according to their needs during infection

Methods

Results

Conclusion