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

  title={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},
  author={Lee-Ann H Allen and Ramona L. McCaffrey},
  journal={Immunological Reviews},
Summary:  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. 

Francisella tularensis Genes Required for Inhibition of the Neutrophil Respiratory Burst and Intramacrophage Growth Identified by Random Transposon Mutagenesis of Strain LVS

It is shown that uracil auxotrophy has cell type-specific effects on the fate of Francisella bacteria, and random transposon mutagenesis is used to identify LVS genes that affect neutrophil activation.

Multifaceted effects of Francisella tularensis on human neutrophil function and lifespan

  • Lauren C. KinkeadL. Allen
  • Biology, Medicine
    Immunological reviews
  • 2016
Current understanding regarding the mechanisms that recruit neutrophils to F. tularensis and distinctive features of the bacterium are reviewed, including its ability to act at a distance to alter overall neutrophil responsiveness to exogenous stimuli, and the evidence which suggests that macrophages and neutrophIL play distinct roles in tularemia pathogenesis.

Loops and networks in control of Francisella tularensis virulence.

The unraveling secrets of the regulatory cascades governing the regulation of virulence of F. tularensis will be discussed along with future challenges yet to be solved.

Antioxidant Defenses of Francisella tularensis Modulate Macrophage Function and Production of Proinflammatory Cytokines*

Novel pathogenic mechanisms adopted by F. tularensis to modulate macrophage innate immune functions to create an environment permissive for its intracellular survival and growth are revealed.

The interaction of Francisella tularensis with lung epithelial cells

Following intranasal inoculation of C57BL/6 mice, Francisella localized to the alveolus and replicated within alveolar type II epithelial cells.

EmrA1 membrane fusion protein of Francisella tularensis LVS is required for resistance to oxidative stress, intramacrophage survival and virulence in mice

The results demonstrate that the emrA1 mutant is highly sensitive to oxidants and several antimicrobial agents, and exhibits diminished intramacrophage growth that can be restored to wild‐type F. tularensis levels by either transcomplementation, inhibition of ROS generation or infection in NADPH oxidase deficient macrophages.

Extracellular adenosine enhances the ability of PMNs to kill Streptococcus pneumoniae by inhibiting IL-10 production

It is demonstrated that CD73 regulates PMN anti-microbial phenotype during pneumococcal pneumonia by promoting the ability of PMNs to kill Streptococcus pneumoniae by blunting IL-10 production.



How do microbes evade neutrophil killing?

Six major strategies that pathogenic bacteria and fungi use to evade neutrophil defences are reviewed, including turning on survival and stress responses, preventing contact, avoiding contact, preventing phagocytosis, surviving intracellularly, and inducing cell death.

Interaction of Campylobacter pyloridis with human immune defence mechanisms.

The in-vitro susceptibility to host immune defence mechanisms of Campylobacter pyloridis was investigated and studies indicated that an intact classical complement pathway was required for optimal phagocytic killing.

Toll-Like Receptor 2 Is Required for Control of Pulmonary Infection with Francisella tularensis

Analysis of pulmonary cytokine levels revealed that TLR2 deficiency results in significantly lower levels of tumor necrosis factor alpha and interleukin-6 but increased amounts of gamma interferon and monocyte chemoattractant protein 1, which may contribute to the exaggerated pathogenesis seen inTLR2−/− mice.

The effect of rebamipide on the expression of proinflammatory mediators and apoptosis in human neutrophils by Helicobacter pylori water‐soluble surface proteins

This data indicates that suppression of cyclooxygenase (COX)‐2 and inhibition of apoptosis in the neutrophils could contribute to the pathogenesis of H. pylori infection.

Atypical Protein Kinase C-ζ Is Essential for Delayed Phagocytosis of Helicobacter pylori

Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape

The data are the first demonstration of a facultative intracellular pathogen, which disrupts the oxidative burst and escapes the phagosome to evade elimination inside neutrophils, and as such, define a novel mechanism of virulence.

Francisella tularensis Selectively Induces Proinflammatory Changes in Endothelial Cells 1

Data indicate that multiple components of F. tularensis LVS induce proinflammatory changes in endothelial cells in an atypical manner that may contribute to the exceptional infectivity and virulence of this pathogen.

Phagocytosis and Killing of Francisella tularensis by Human Polymorphonuclear Leukocytes

Bacteria of a wild strain of Francisella tularensis were less efficiently killed by human polymorphonuclear leukocytes than were bacteria of an attenuated strain, but bacteria of the wild strain also seemed to be more resistant to killing after ingestion.

The Neutrophil-Activating Protein (Hp-Nap) of Helicobacter pylori Is a Protective Antigen and a Major Virulence Factor

It is shown that vaccination of mice with HP-NAP induces protection against H. pylori challenge, and that the majority of infected patients produce antibodies specific for HP-nAP, suggesting an important role of this factor in immunity.

Anaplasma phagocytophilum Utilizes Multiple Host Evasion Mechanisms To Thwart NADPH Oxidase-Mediated Killing during Neutrophil Infection

Anaplasma phagocytophilum employs at least two strategies to protect itself from neutrophil NADPH oxidase-mediated killing, and may scavenge exogenous O2− in a cell-free system.