The Interplay of Host Lysosomes and Intracellular Pathogens.

Kuldeep Sachdeva,Varadharajan Sundaramurthy

doi:10.3389/fcimb.2020.595502

Abstract

Lysosomes are an integral part of the intracellular defense system against microbes. Lysosomal homeostasis in the host is adaptable and responds to conditions such as infection or nutritional deprivation. Pathogens such as Mycobacterium tuberculosis (Mtb) and Salmonella avoid lysosomal targeting by actively manipulating the host vesicular trafficking and reside in a vacuole altered from the default lysosomal trafficking. In this review, the mechanisms by which the respective pathogen containing vacuoles (PCVs) intersect with lysosomal trafficking pathways and maintain their distinctness are discussed. Despite such active inhibition of lysosomal targeting, emerging literature shows that different pathogens or pathogen derived products exhibit a global influence on the host lysosomal system. Pathogen mediated lysosomal enrichment promotes the trafficking of a sub-set of pathogens to lysosomes, indicating heterogeneity in the host-pathogen encounter. This review integrates recent advancements on the global lysosomal alterations upon infections and the host protective role of the lysosomes against these pathogens. The review also briefly discusses the heterogeneity in the lysosomal targeting of these pathogens and the possible mechanisms and consequences.

Highlights

Reviewed by: Thorsten Maretzky, The University of Iowa, United States Surya Prakash Pandey, University of Pittsburgh, United States
Lysosomal homeostasis in the host is adaptable and responds to conditions such as infection or nutritional deprivation. Pathogens such as Mycobacterium tuberculosis (Mtb) and Salmonella avoid lysosomal targeting by actively manipulating the host vesicular trafficking and reside in a vacuole altered from the default lysosomal trafficking
Several other studies have reported that the chemical or genetic enrichment of lysosomes enhances bactericidal properties and bacterial clearance of other pathogens such as Burkholderia cenocepacia, methicillin-resistant Staphylococcus aureus and enteroinvasive Escherichia coli (Sogi et al, 2017; Vural et al, 2018; Liu et al, 2019). These studies show an emerging consensus with these limited examples of the global content of lysosomes in cells having a growth inhibitory effect on intracellular pathogens. While these studies show the relevance of global alteration of lysosomes to the infection, our recent study throws light on lysosomal heterogeneity influencing intracellular Mtb trafficking in a non-perturbed macrophage population, i.e a higher proportion of Mtb are delivered to lysosomes in cells with higher lysosomal content (Sachdeva et al, 2020a; Sachdeva et al, 2020b)

Summary

Introduction

Reviewed by: Thorsten Maretzky, The University of Iowa, United States Surya Prakash Pandey, University of Pittsburgh, United States. This review integrates recent advancements on the global lysosomal alterations upon infections and the host protective role of the lysosomes against these pathogens. These studies show that bacterial membrane components have an influence on the signaling pathways regulating lysosomal homeostasis of the host cells (Hipolito et al, 2019; Najibi et al, 2019; Sachdeva et al, 2020a), and exert an effect on lysosomes globally in the infected cell, beyond the confines of the PCV’s.

Results

Conclusion