Luminescent-Activated Transfected Killer Cells to Monitor Leukocyte Trafficking During Systemic Bacterial and Fungal Infection

Lin, Lin; Ibrahim, Ashraf S.; Baquir, Beverlie; Palosaari, Andrew; Spellberg, Brad

doi:10.1093/infdis/jir725

Cited by 12 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of our current knowledge about neutrophil function in the setting of A. baumannii infection originates from mice treated with cyclophosphamide, ( Qiu et al, 2009 ; Lin et al, 2012 ; Manepalli et al, 2013 ; Thompson et al, 2014 ; Bruhn et al, 2015 ) a cytotoxic alkylating agent widely used for the treatment of neoplastic and severe autoimmune diseases. Cyclophosphamide suppresses myelopoiesis resulting in neutrophil depletion in murine models ( Zuluaga et al, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

Neutropenia exacerbates infection by Acinetobacter baumannii clinical isolates in a murine wound model

et al. 2015

View full text Add to dashboard Cite

The Gram negative coccobacillus Acinetobacter baumannii has become an increasingly prevalent cause of hospital-acquired infections in recent years. The majority of clinical A. baumannii isolates display high-level resistance to antimicrobials, which severely compromises our capacity to care for patients with A. baumannii disease. Neutrophils are of major importance in the host defense against microbial infections. However, the contribution of these cells of innate immunity in host resistance to cutaneous A. baumannii infection has not been directly investigated. Hence, we hypothesized that depletion of neutrophils increases severity of bacterial disease in an experimental A. baumannii murine wound model. In this study, the Ly-6G-specific monoclonal antibody (mAb), 1A8, was used to generate neutropenic mice and the pathogenesis of several A. baumannii clinical isolates on wounded cutaneous tissue was investigated. We demonstrated that neutrophil depletion enhances bacterial burden using colony forming unit determinations. Also, mAb 1A8 reduces global measurements of wound healing in A. baumannii-infected animals. Interestingly, histological analysis of cutaneous tissue excised from A. baumannii-infected animals treated with mAb 1A8 displays enhanced collagen deposition. Furthermore, neutropenia and A. baumannii infection alter pro-inflammatory cytokine release leading to severe microbial disease. Our findings provide a better understanding of the impact of these innate immune cells in controlling A. baumannii skin infections.

show abstract

Section: Introductionmentioning

confidence: 99%

Neutropenia exacerbates infection by Acinetobacter baumannii clinical isolates in a murine wound model

et al. 2015

View full text Add to dashboard Cite

show abstract

“…cerevisiae and in other pathogenic organisms such as C . albicans [ 16 ], [ 24 ], [ 32 ]. The results revealed that only 15% of mice infected with strain D14 survive until day 22, whereas D14Δgua1 was unable to cause death in the mice.…”

Section: Resultsmentioning

confidence: 99%

Comparative Genomic Analysis Reveals a Critical Role of De Novo Nucleotide Biosynthesis for Saccharomyces cerevisiae Virulence

et al. 2015

View full text Add to dashboard Cite

In recent years, the number of human infection cases produced by the food related species Saccharomyces cerevisiae has increased. Whereas many strains of this species are considered safe, other ‘opportunistic’ strains show a high degree of potential virulence attributes and can cause infections in immunocompromised patients. Here we studied the genetic characteristics of selected opportunistic strains isolated from dietary supplements and also from patients by array comparative genomic hybridization. Our results show increased copy numbers of IMD genes in opportunistic strains, which are implicated in the de novo biosynthesis of the purine nucleotides pathway. The importance of this pathway for virulence of S. cerevisiae was confirmed by infections in immunodeficient murine models using a GUA1 mutant, a key gene of this pathway. We show that exogenous guanine, an end product of this pathway in its triphosphorylated form, increases the survival of yeast strains in ex vivo blood infections. Finally, we show the importance of the DNA damage response that activates dNTP biosynthesis in yeast cells during ex vivo blood infections. We conclude that opportunistic yeasts may use an enhanced de novo biosynthesis of the purine nucleotides pathway to increase survival and favor infections in the host.

show abstract

“…Antifungal therapy failured to manage the infection due to the presence of hyphae, the main feature of the fungus that allows it to penetrate blood vessels, and this prevents the penetration of antifungal agents into the fungus (Mehrad et al, ). Studies conducted have shown that neutrophils display potent anti‐ Aspergillus activity, exhibiting efficient migration to sites of fungal infection (Farowski et al, ; Lin et al, ; Lin, Ibrahim, Baquir, Palosaari, & Spellberg, ; Todeschini et al, ). It has been also found that posaconazole, a broad‐spectrum antifungal, accumulates in large concentrations in leukocytes, especially in neutrophils (Campoli et al, ; Conte Jr. et al, ; Hof, ).…”

Section: Neutrophil‐targeted Drug Delivery In Respiratory Diseasesmentioning

confidence: 99%

Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases

Chellappan

Yee

Xuan

et al. 2020

Drug Development Research

View full text Add to dashboard Cite

Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy. K E Y W O R D S nanoparticle, neutrophils, novel drug delivery, pulmonary, respiratory diseases

show abstract

Luminescent-Activated Transfected Killer Cells to Monitor Leukocyte Trafficking During Systemic Bacterial and Fungal Infection

Abstract: ATAK cells accumulated in target organs with distinct profiles, depending on the microbial etiology of infection. Finally, generation of an anti-ATAK immune response may provide an important safety mechanism that helps clear the cells from the host as the marrow recovers.

Cited by 12 publications

References 27 publications

Neutropenia exacerbates infection by Acinetobacter baumannii clinical isolates in a murine wound model

Neutropenia exacerbates infection by Acinetobacter baumannii clinical isolates in a murine wound model

Comparative Genomic Analysis Reveals a Critical Role of De Novo Nucleotide Biosynthesis for Saccharomyces cerevisiae Virulence

Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases

Contact Info

Product

Resources

About