Mechanisms controlling bacterial infection in myeloid cells under hypoxic conditions

Abstract

Various factors of the tissue microenvironment such as the oxygen concentration influence the host–pathogen interaction. During the past decade, hypoxia-driven signaling via hypoxia-inducible factors (HIF) has emerged as an important factor that affects both the pathogen and the host. In this chapter, we will review the current knowledge of this complex interplay, with a particular emphasis given to the impact of hypoxia and HIF on the inflammatory and antimicrobial activity of myeloid cells, the bacterial responses to hypoxia and the containment of bacterial infections under oxygen-limited conditions. We will also summarize how low oxygen concentrations influence the metabolism of neutrophils, macrophages and dendritic cells. Finally, we will discuss the consequences of hypoxia and HIFα activation for the invading pathogen, with a focus on Pseudomonas aeruginosa, Mycobacterium tuberculosis, Coxiella burnetii, Salmonella enterica and Staphylococcus aureus. This includes a description of the mechanisms and microbial factors, which the pathogens use to sense and react to hypoxic conditions.

Acidic Microenvironments Found in Cutaneous Leishmania Lesions Curtail NO-Dependent Antiparasitic Macrophage Activity

“…The mechanisms that trigger low tissue pH warrant further investigation. For instance, following and extending earlier reasoning [reviewed in: ( 10 )], it is possible that infection-associated cell death [reviewed in: ( 53 )], infection-induced increases in glycolysis and metabolic reprogramming [reviewed in: ( 12 )] and/or infection-triggered induction of low tissue oxygen [reviewed in: ( 6 )] contribute to low tissue pH.…”

“…Immune responses in infected tissues are not only driven by inflammatory cytokines and mediators, but also by local ionic composition [reviewed in: ( 1 )], metabolism ( 2 – 5 ), and oxygen availability [reviewed in: ( 6 – 8 )]. Hypoxia is a hallmark of infected tissue [reviewed in: ( 6 – 9 )]. It triggers anaerobic glycolysis which ultimately contributes to lactic acid production [reviewed in: ( 10 , 11 )].…”

Stabilization of Hypoxia-Inducible Factor Promotes Antimicrobial Activity of Human Macrophages Against Mycobacterium tuberculosis

“…However, HIF-1-α is a ubiquitous transcription factor which is expressed in all myeloid cells including macrophages. The genes responding to HIF-1-α are highly diverse and include the regulation of metabolism, cell division and immune functions ( 6 ). The functional impact of gene regulation does not follow a predictable pattern and the understanding of biological end points (e.g.…”

“…HIFs are not only sensors for cellular hypoxia, but also control key functions of immune cells required for protection against microbial pathogens ( 5 , 6 ). Though several HIF isoforms exist, HIF-1α is the most prominent and detected nearly in all innate immune populations ( 7 ).…”

Immune Modulation by Inhibitors of the HO System

“…The contribution of HO-1 during bacterial infection could be beneficial or harmful depending on the infecting pathogen, as pointed out below in the section. Myeloid cells are one of the first lines of defense, and they constitute critical players during an immune response to bacterial infections [133]. Accordingly, the performance of these cells can profoundly impact the efficiency of adaptive immunity.…”