To activate or not to activate: distinct strategies used by Helicobacter pylori and Francisella tularensis to modulate the NADPH oxidase and survive in human neutrophils

Abstract

Neutrophils accumulate rapidly at sites of infection, and the ability of these cells to phagocytose and kill microorganisms is an essential component of the innate immune response. Relatively few microbial pathogens are able to evade neutrophil killing. Herein, we describe the novel strategies used by Helicobacter pylori and Francisella tularensis to disrupt neutrophil function, with a focus on assembly and activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.

In-vivo evaluation of apocynin for prevention of Helicobacter pylori-induced gastric carcinogenesis

“…In addition, H. pylori directs NADPH oxidase (NOX) targeting towards the cell membrane, which results in the massive release of superoxide radicals (O 2 •-) in the extracellular space. As such, persistently infected stomach tissue is continuously exposed to cytotoxic bacterial virulence factors and ROS (Allen and McCaffrey, 2007). Depending on multiple bacterial, immunological and environmental factors, H. pylori infection leads to a variety of clinical outcomes, ranging from asymptomatic chronic gastritis over gastric ulcers to gastric carcinoma or lymphoma (Allen and McCaffrey, 2007;Hardbower et al, 2013).…”

“…As such, persistently infected stomach tissue is continuously exposed to cytotoxic bacterial virulence factors and ROS (Allen and McCaffrey, 2007). Depending on multiple bacterial, immunological and environmental factors, H. pylori infection leads to a variety of clinical outcomes, ranging from asymptomatic chronic gastritis over gastric ulcers to gastric carcinoma or lymphoma (Allen and McCaffrey, 2007;Hardbower et al, 2013). Since 10 to 20% of H. pylori-infected individuals develop significant morbidity, current treatment guidelines aim to clear the infection immediately after diagnosis using a combination of two antibiotics and a proton pump inhibitor (Malfertheiner et al, 2012).…”

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

“…Following receptor-mediated phagocytosis of microbes, neutrophils are activated and utilize both oxygen-dependent and oxygen-independent killing mechanisms to kill their target (143,(273)(274)(275). The focus of our studies is on the oxygen-dependent respiratory burst response employed by human neutrophils in response to F. alocis challenge.…”

“…The respiratory burst response by neutrophils is named so due to the rapid increase in oxygen consumption by activated neutrophils and results from a step-wise production of superoxide from the NADPH oxidase complex which dismutates and yields H2O2, and in the presence of MPO and chloride, the potent HOCl is produced (143,270,281). The timing of superoxide production and whether this occurs at the plasma membrane or the phagosome depends on the type of stimulus encountered (282,283).…”

“…The NADPH oxidase complex can assemble at the cell membrane if the neutrophil encounters a soluble (ex: fMLF) stimulus or at the phagosomal membrane when encountering a particulate stimulus (ex: bacteria or yeast) and further will generate superoxide release into the extracellular environment or phagosomal compartment, respectively (143,144). NADPH oxidase activity takes place in three stages: 1) initiation by assembly and activation, 2) maintenance of activation, 3) deactivation of the response through component disassembly (145).…”