Assessment of the Glycan-Binding Profile of Pseudomonas aeruginosa PAO1.

Pseudomonas aeruginosa is an opportunistic pathogen that can establish acute and chronic infections in individuals who lack fully functional innate immunity. In particular, phagocytosis by neutrophils and macrophages is a key mechanism that modulates host control and clearance of P. aeruginosa.

Assessment of the Glycan-Binding Profile of PAO1.

Unlabelled: is an opportunistic pathogen that can establish acute and chronic infections in individuals that lack fully functional innate immunity. In particular, phagocytosis by neutrophils and macrophages is a key mechanism that modulates host control and clearance of . Individuals with neutropenia or cystic fibrosis are highly susceptible to infection thus underscoring the importance of the host innate immune response.

Cisplatin increases immune activity of monocytes and cytotoxic T-cells in a murine model of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is an immunologically active malignancy, but thus far immune therapy has had limited success in clinical trials. One barrier to implementation of efficacious immune therapies is a lack of knowledge of the effect of chemotherapy on the monocyte-derived component of the immune infiltrate within the tumor. We utilized the ID8 murine EOC model to investigate alterations within tumor ascites that occur following administration of platinum chemotherapy.

Identification of cell-surface glycans that mediate motility-dependent binding and internalization of Pseudomonas aeruginosa by phagocytes.

Phagocytic cells are critical to host defense against Pseudomonas aeruginosa, a Gram-negative bacterium that is an opportunistic pathogen. Accordingly, susceptible individuals frequently have impaired innate immune responses, including those with cystic fibrosis or neutropenia. Previous studies identified that the downregulation, or loss, of bacterial flagellar motility enables bacteria to evade interactions with phagocytic cells that result in phagocytic uptake of the bacteria.

Identifying in vivo inflammation using magnetic nanoparticle spectra.

We are developing magnetic nanoparticle (NP) methods to characterize inflammation and infection in vivo. Peritoneal infection in C57BL/6 mice was used as a biological model. An intraperitoneal NP injection was followed by measurement of magnetic nanoparticle spectroscopy of Brownian rotation (MSB) spectra taken over time.

Distinct Contributions of CD18 Integrins for Binding and Phagocytic Internalization of Pseudomonas aeruginosa.

Phagocytosis is the key mechanism for host control of , a motile Gram-negative, opportunistic bacterial pathogen which frequently undergoes adaptation and selection for traits that are advantageous for survival. One such clinically relevant adaptation is the loss of bacterial motility, observed within chronic infections, that is associated with increased antibiotic tolerance and phagocytic resistance. Previous studies using phagocytes from a leukocyte adhesion deficiency type 1 (LAD-I) patient identified CD18 as a putative cell surface receptor for uptake of live However, how bacterial motility alters direct engagement with CD18-containing integrins remains unknown.

Regulation of -Mediated Neutrophil Extracellular Traps.

is the most prevalent opportunistic pathogen in the airways of cystic fibrosis (CF) patients. The pulmonary disorder is characterized by recurrent microbial infections and an exaggerated host inflammatory immune response led primarily by influx of neutrophils. Under these conditions, chronic colonization with is associated with diminished pulmonary function and increased morbidity and mortality.

Motility-Independent Formation of Antibiotic-Tolerant Pseudomonas aeruginosa Aggregates.

is a bacterial pathogen that causes severe chronic infections in immunocompromised individuals. This bacterium is highly adaptable to its environments, which frequently select for traits that promote bacterial persistence. A clinically significant temporal adaptation is the formation of surface- or cell-adhered bacterial biofilms that are associated with increased resistance to immune and antibiotic clearance.

A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases.

Epithelial ovarian cancer (EOC) is a deadly gynecologic malignancy, but animal models for the study of EOC pathophysiology and drug efficacy are limited. Based on the finding that women with EOC are at risk for metastasis at a trocar site after laparoscopy, we developed a syngeneic murine model of port-site metastasis of EOC. We leveraged the ID8 murine EOC cell line to induce intra-peritoneal tumors in mice.

Guanylate binding proteins facilitate caspase-11-dependent pyroptosis in response to type 3 secretion system-negative .

Detection of bacterial ligands is a pre-requisite for inflammasome activation. During infection, flagellin which is secreted through the T3SS is detected by the NLRC4 inflammasome. Activation of the NLRC4 inflammasome is believed to contribute to high IL-1β production and pathogenicity in cystic fibrosis patients with chronic infection.

Phosphatidylinositol-(3,4,5)-Trisphosphate Induces Phagocytosis of Nonmotile Pseudomonas aeruginosa.

Pathogenic bacteria that establish chronic infections in immunocompromised patients frequently undergo adaptation or selection for traits that are advantageous for their growth and survival. Clinical isolates of , a Gram-negative, opportunistic bacterial pathogen, exhibit a temporal transition from a motile to a nonmotile phenotype through loss of flagellar motility during the course of chronic infection. This progressive loss of motility is associated with increased resistance to both antibiotic and immune clearance.

Evaluating blood clot progression using magnetic particle spectroscopy.

Purpose: To evaluate the thrombus maturity noninvasively providing the promise of much earlier and more accurate diagnosis of diseases ranging from stroke to myocardial infarction to deep vein thrombosis.

Methods: Magnetic spectroscopy of nanoparticle Brownian rotation (MSB), a form of magnetic particle spectroscopy sensitive to Brownian rotation of magnetic nanoparticles, was used for the detection and characterization of blood clots. The nanoparticles' relaxation time was quantified by scaling the MSB spectra in frequency to match the spectra from nanoparticles in a reference state.

Lumacaftor (VX-809) restores the ability of CF macrophages to phagocytose and kill Pseudomonas aeruginosa.

Cystic fibrosis (CF), the most common lethal genetic disease in Caucasians, is characterized by chronic bacterial lung infection and excessive inflammation, which lead to progressive loss of lung function and premature death. Although ivacaftor (VX-770) alone and ivacaftor in combination with lumacaftor (VX-809) improve lung function in CF patients with the Gly551Asp and del508Phe mutations, respectively, the effects of these drugs on the function of human CF macrophages are unknown. Thus studies were conducted to examine the effects of lumacaftor alone and lumacaftor in combination with ivacaftor (i.

The effect of loss of O-antigen ligase on phagocytic susceptibility of motile and non-motile Pseudomonas aeruginosa.

The bacterial pathogen Pseudomonas aeruginosa undergoes adaptation and selection over the course of chronic respiratory tract infections which results in repeatedly-observed phenotypic changes that are proposed to enable its persistence. Two of the clinically significant P. aeruginosa phenotypic changes are loss of flagellar motility and modifications to LPS structure, including loss of O-antigen expression.

Acidosis exacerbates in vivo IL-1-dependent inflammatory responses and neutrophil recruitment during pulmonary Pseudomonas aeruginosa infection.

Acidic microenvironments commonly occur at sites of inflammation and bacterial infections. In the context of a Pseudomonas aeruginosa infection, we previously demonstrated that acidosis enhances the cellular proinflammatory interleukin (IL)-1β response in vitro. However, how pH alterations affect in vivo IL-1β responses and subsequent IL-1-driven inflammation during infection with P.

Acidosis increases the susceptibility of respiratory epithelial cells to -induced cytotoxicity.

Bacterial infection can lead to acidosis of the local microenvironment, which is believed to exacerbate disease pathogenesis; however, the mechanisms by which changes in pH alter disease progression are poorly understood. We test the hypothesis that acidosis enhances respiratory epithelial cell death in response to infection with Our findings support the idea that acidosis in the context of infection results in increased epithelial cell cytotoxicity due to ExoU intoxication. Importantly, enforced maintenance of neutral pH during infection demonstrates that cytotoxicity is dependent on the acidosis.

Blood clot detection using magnetic nanoparticles.

Deep vein thrombosis, the development of blood clots in the peripheral veins, is a very serious, life threatening condition that is prevalent in the elderly. To deliver proper treatment that enhances the survival rate, it is very important to detect thrombi early and at the point of care. We explored the ability of magnetic particle spectroscopy (MSB) to detect thrombus via specific binding of aptamer functionalized magnetic nanoparticles with the blood clot.

Monomethylarsonous Acid (MMAIII) Has an Adverse Effect on the Innate Immune Response of Human Bronchial Epithelial Cells to Pseudomonas aeruginosa.

Unlabelled: Arsenic is the number one contaminant of concern with regard to human health according to the World Health Organization. Epidemiological studies on Asian and South American populations have linked arsenic exposure with an increased incidence of lung disease, including pneumonia, and chronic obstructive pulmonary disease, both of which are associated with bacterial infection. However, little is known about the effects of low dose arsenic exposure, or the contributions of organic arsenic to the innate immune response to bacterial infection.

Differential ASC requirements reveal a key role for neutrophils and a noncanonical IL-1β response to Pseudomonas aeruginosa.

The NLRC4 inflammasome is responsible for IL-1β processing by macrophages in response to Pseudomonas aeruginosa infection. We therefore hypothesized that mice that lack ASC, an NLRC4 inflammasome adaptor protein necessary for in vitro IL-1β production by macrophages, would be preferentially protected from a hyperinflammatory lethal challenge that is dependent on bacterial type three secretion system (T3SS) activity. We report herein that lack of ASC does not confer preferential protection in response to P.

Structure-based redesign of lysostaphin yields potent antistaphylococcal enzymes that evade immune cell surveillance.

Staphylococcus aureus infections exert a tremendous burden on the health-care system, and the threat of drug-resistant strains continues to grow. The bacteriolytic enzyme lysostaphin is a potent antistaphylococcal agent with proven efficacy against both drug-sensitive and drug-resistant strains; however, the enzyme's own bacterial origins cause undesirable immunogenicity and pose a barrier to clinical translation. Here, we deimmunized lysostaphin using a computationally guided process that optimizes sets of mutations to delete immunogenic T cell epitopes without disrupting protein function.

Myeloid derived hypoxia inducible factor 1-alpha is required for protection against pulmonary Aspergillus fumigatus infection.

Hypoxia inducible factor 1α (HIF1α) is the mammalian transcriptional factor that controls metabolism, survival, and innate immunity in response to inflammation and low oxygen. Previous work established that generation of hypoxic microenvironments occurs within the lung during infection with the human fungal pathogen Aspergillus fumigatus. Here we demonstrate that A.

Acidosis potentiates the host proinflammatory interleukin-1β response to Pseudomonas aeruginosa infection.

Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood.

CX3CR1 delineates temporally and functionally distinct subsets of myeloid-derived suppressor cells in a mouse model of ovarian cancer.

Expression of the chemokine receptor CX3CR1 has been used to identify distinct populations within the monocyte, macrophage and dendritic cell lineages. Recent evidence indicates that CX3CR1-positive subsets of myeloid cells play distinct and important roles in a wide range of immunological maladies, and thus the use of CX3CR1 expression has leveraged our understanding of the myeloid contribution to a multitude of diseases. Here we use CX3CR1 expression as a means to identify a novel nongranulocytic CX3CR1-negative myeloid population that is functionally distinct from the previously described CX3CR1-positive cellular subsets within the CD11b-positive cellular compartment of ascites from ovarian tumor-bearing mice.