Influence of Neutrophil Defects on Burkholderia cepacia Complex Pathogenesis

Porter, Laura A.; Goldberg, Joanna B.

doi:10.3389/fcimb.2011.00009

Cited by 11 publications

(7 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pathogens include P. aeruginosa, Burkholderia cepacia, S. aureus, and Haemophilus influenzae. It is noteworthy that the proclivity of patients with CF for infections with B. cepacia and with S. aureus overlaps with the spectrum of pathogens seen in patients with CGD [127,128], an inherited impairment of NOX [129][130][131]. Given the evidence indicating defective neutrophil function in patients with CF, the parallel between CGD and CF is intriguing, although patients with CGD experience frequent and severe infections in organ systems other than the lung, whereas infectious complications in CF are largely restricted to the airways.…”

Section: Cftr Chloride Channel and Host Defensementioning

confidence: 99%

Salt, chloride, bleach, and innate host defense

Wang

Nauseef

2015

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense.

show abstract

Section: Cftr Chloride Channel and Host Defensementioning

confidence: 99%

Salt, chloride, bleach, and innate host defense

Wang

Nauseef

2015

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…Despite B. cenocepacia mechanisms to scavenge ROS of host cells, these bacteria succumb to ROS-dependent killing mechanisms upon efficient neutrophil responses in healthy individuals. However patients with chronic granulomatous disease (CGD), which is characterized by defective NADPH oxidase, are highly susceptible to develop infections by B. cenocepacia (20). Similar susceptibility of CF patients to B. cenocepacia infections has led investigators to search for abnormalities in the oxidative responses of the CF neutrophil.…”

Section: Introductionmentioning

confidence: 99%

Dysregulated Calcium Homeostasis in Cystic Fibrosis Neutrophils Leads to Deficient Antimicrobial Responses

Robledo‐Avila

Ruíz-Rosado

Brockman

et al. 2018

The Journal of Immunology

View full text Add to dashboard Cite

Cystic fibrosis (CF), one of the most common human genetic diseases worldwide, is caused by a defect in the CF transmembrane conductance regulator (CFTR). Patients with CF are highly susceptible to infections caused by opportunistic pathogens (including ), which induce excessive lung inflammation and lead to the eventual loss of pulmonary function. Abundant neutrophil recruitment into the lung is a key characteristic of bacterial infections in CF patients. In response to infection, inflammatory neutrophils release reactive oxygen species and toxic proteins, leading to aggravated lung tissue damage in patients with CF. The present study shows a defect in reactive oxygen species production by mouse , human F508del-CFTR, and CF neutrophils; this results in reduced antimicrobial activity against Furthermore, dysregulated Ca homeostasis led to increased intracellular concentrations of Ca that correlated with significantly diminished NADPH oxidase response and impaired secretion of neutrophil extracellular traps in human CF neutrophils. Functionally deficient human CF neutrophils recovered their antimicrobial killing capacity following treatment with pharmacological inhibitors of Ca channels and CFTR channel potentiators. Our findings suggest that regulation of neutrophil Ca homeostasis (via CFTR potentiation or by the regulation of Ca channels) can be used as a new therapeutic approach for reestablishing immune function in patients with CF.

show abstract

“…During the course of an infection, Bcc must combat the innate immune system in order to persist. Because of the prevalence of Bcc as CGD pathogens and the fact that CGD patients have defects in oxidative killing mechanisms, it is hypothesized that this mechanism of killing by host phagocytes is essential for Bcc clearance in healthy individuals (Zelazny et al ., ; Greenberg et al ., ) and reviewed in Porter and Goldberg (). Superoxide dismutases and catalases are enzymes commonly used to protect bacteria from oxidative damage during normal respiration and in interactions with the host innate immune response, but pathogens can also utilize additional factors that assist in protection from host oxidative killing mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Single amino acid substitution in homogentisate 1,2‐dioxygenase is responsible for pigmentation in a subset of Burkholderia cepacia complex isolates

Gonyar

Fankhauser

Goldberg

2014

Environ Microbiol Rep

Self Cite

View full text Add to dashboard Cite

Summary The Burkholderia cepacia complex (Bcc) is a group of Gram-negative bacilli that are ubiquitous in the environment and have emerged over the past 30 years as opportunistic pathogens in immunocompromised populations, specifically individuals with cystic fibrosis (CF) and chronic granulomatous disease. This complex of at least 18 distinct species is phenotypically and genetically diverse. One phenotype observed in a subset of Burkholderia cenocepacia (a prominent Bcc pathogen) isolates is the ability to produce a melanin-like pigment. Melanins have antioxidant properties and have been shown to act as virulence factors allowing pathogens to resist killing by the host immune system. The melanin-like pigment expressed by B. cenocepacia is produced through tyrosine catabolism, specifically through the autoxidation and polymerization of homogentisate. Burkholderia cenocepacia J2315 is a CF clinical isolate that displays a pigmented phenotype when grown under normal laboratory conditions. We examined the amino acid sequences of critical enzymes in the melanin synthesis pathway in pigmented and non-pigmented Bcc isolates, and found that an amino acid substitution of glycine for arginine at amino acid 378 in homogentisate 1,2-dioxygenase correlated with pigment production; we identify this as one mechanism for expression of pigment in Bcc isolates.

show abstract

Influence of Neutrophil Defects on Burkholderia cepacia Complex Pathogenesis

Cited by 11 publications

References 107 publications

Salt, chloride, bleach, and innate host defense

Salt, chloride, bleach, and innate host defense

Dysregulated Calcium Homeostasis in Cystic Fibrosis Neutrophils Leads to Deficient Antimicrobial Responses

Single amino acid substitution in homogentisate 1,2‐dioxygenase is responsible for pigmentation in a subset of Burkholderia cepacia complex isolates

Contact Info

Product

Resources

About