Pathogens MenTORing Macrophages and Dendritic Cells: Manipulation of mTOR and Cellular Metabolism to Promote Immune Escape

Lonneke V Nouwen, Bart Everts, Lonneke V Nouwen, Bart Everts

Abstract

Myeloid cells, including macrophages and dendritic cells, represent an important first line of defense against infections. Upon recognition of pathogens, these cells undergo a metabolic reprogramming that supports their activation and ability to respond to the invading pathogens. An important metabolic regulator of these cells is mammalian target of rapamycin (mTOR). During infection, pathogens use host metabolic pathways to scavenge host nutrients, as well as target metabolic pathways for subversion of the host immune response that together facilitate pathogen survival. Given the pivotal role of mTOR in controlling metabolism and DC and macrophage function, pathogens have evolved strategies to target this pathway to manipulate these cells. This review seeks to discuss the most recent insights into how pathogens target DC and macrophage metabolism to subvert potential deleterious immune responses against them, by focusing on the metabolic pathways that are known to regulate and to be regulated by mTOR signaling including amino acid, lipid and carbohydrate metabolism, and autophagy.

Keywords: cellular metabolism; dendritic cells; immune escape; mTOR; macrophages; pathogens.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Strategies that pathogens use to directly target mTOR.
Figure 2
Figure 2
Overview of metabolic targets through which pathogens are known to modulate DC and macrophage functions. In (A–D), the key strategies through which different pathogens modulate (A) amino acid metabolism, (B) lipid metabolism, (C) carbohydrate metabolism and (D) other mTOR-controlled processes in DCs and macrophages to promote immune evasion are indicated Blue = pathogens involved; Red = inhibition by pathogens; Green = stimulation by pathogens..
Figure 3
Figure 3
L-arginine is metabolized by iNOS and Arginase, creating competition between pathogen clearance and survival by modulating immune responses through the production of NO and polyamines. The dashed arrow represents a process only observed in trypanosomatid parasites.

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Source: PubMed

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