In tissues, neutrophils neutralize Candida albicans through phagocytosis and delay C. albicans hyphae growth by deploying neutrophil extracellular traps (NETs). However, in the bloodstream, the dynamic interactions between NETs and C.
View Article and Find Full Text PDFUnlabelled: Neutrophils communicate with one another and amplify their destructive power through swarming, a collective process that synchronizes the activities of multiple neutrophils against one target. The sequence of activities contributing to swarming against clusters of fungi has been recently uncovered. However, the molecular signals controlling the neutrophils' activities during the swarming process are just emerging.
View Article and Find Full Text PDFThe intermediate filament vimentin is present in immune cells and is implicated in proinflammatory immune responses. Whether and how it supports antimicrobial activities of neutrophils are not well established. Here, we developed an immortalized neutrophil model to examine the requirement of vimentin.
View Article and Find Full Text PDFUnlabelled: Infection control measures to prevent viral and bacterial infection spread are critical to maintaining a healthy environment. Pathogens such as viruses and pyogenic bacteria can cause infectious complications. Viruses such as SARS-CoV-2 are known to spread through the aerosol route and on fomite surfaces, lasting for a prolonged time in the environment.
View Article and Find Full Text PDFAs the leading cause of fungal skin infections around the globe, dermatophytes are responsible for a multitude of skin ailments, ranging from athlete's foot to ringworm. Due to the combination of its growing prevalence and antifungal misuse, antifungal-resistant dermatophyte strains like have begun to emerge, posing a significant global health risk. The emergence of these resistant dermatophytes highlights a critical need to identify alternative methods of treating dermatophyte infections.
View Article and Find Full Text PDF(), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant three-fold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread.
View Article and Find Full Text PDFNeutrophils collectively migrate to sites of injury and infection. How these swarms are coordinated to ensure the proper level of recruitment is unknown. Using an ex vivo model of infection, we show that human neutrophil swarming is organized by multiple pulsatile chemoattractant waves.
View Article and Find Full Text PDFInhibition of Bruton's tyrosine kinase (BTK) through covalent modifications of its active site (e.g., ibrutinib [IBT]) is a preferred treatment for multiple B cell malignancies.
View Article and Find Full Text PDFThe intermediate filament vimentin is present in immune cells and is implicated in proinflammatory immune responses. Whether and how it supports antimicrobial activities of neutrophils is not well established. Here, we developed an immortalized neutrophil model to examine the requirement of vimentin.
View Article and Find Full Text PDFUnlabelled: Recent epidemiological studies documented an alarming increase in the prevalence of echinocandin-resistant (ECR) blood isolates. ECR isolates are known to arise from a minor subpopulation of a clonal population, termed echinocandin persisters. Although it is believed that isolates with a higher echinocandin persistence (ECP) are more likely to develop ECR, the implication of ECP needs to be better understood.
View Article and Find Full Text PDFMolecular mechanisms driving clonal aggressiveness in leukemia are not fully understood. We tracked and analyzed MLL-rearranged leukemic clones independently evolving towards higher aggressiveness. More aggressive subclones lost their growth differential ex vivo but restored it upon secondary transplantation, suggesting molecular memory of aggressiveness.
View Article and Find Full Text PDFDisruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose.
View Article and Find Full Text PDFis known to cause severe and persistent outbreaks in clinical settings. Patients infected with multidrug-resistant (MDR Cp) isolates were identified in a large Turkish hospital from 2017-2020. We subsequently identified three additional patients infected with MDR Cp isolates in 2022 from the same hospital and two echinocandin-resistant (ECR) isolates from a single patient in another hospital.
View Article and Find Full Text PDFThe host type I interferon (IFN) pathway is a major signature of inflammation induced by the human fungal pathogen, Candida albicans. However, the molecular mechanism for activating this pathway in the host defence against C. albicans remains unknown.
View Article and Find Full Text PDFPatients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring invasive fungal infections (IFIs). These infections carry high morbidity and mortality. Multiple factors, including host immune dysfunction, barrier failures, malnutrition, and microbiome alterations, increase the risk of developing IFI.
View Article and Find Full Text PDFNeutrophils exhibit self-amplified swarming to sites of injury and infection. How swarming is controlled to ensure the proper level of neutrophil recruitment is unknown. Using an model of infection, we find that human neutrophils use active relay to generate multiple pulsatile waves of swarming signals.
View Article and Find Full Text PDFMyeloid cell heterogeneity is known, but whether it is cell-intrinsic or environmentally-directed remains unclear. Here, an inducible/reversible system pausing myeloid differentiation allowed the definition of clone-specific functions that clustered monocytes into subsets with distinctive molecular features. These subsets were orthogonal to the classical/nonclassical categorization and had inherent, restricted characteristics that did not shift under homeostasis, after irradiation, or with infectious stress.
View Article and Find Full Text PDFCandida parapsilosis is a significant cause of candidemia worldwide. Echinocandin-resistant (ECR) and echinocandin-tolerant (ECT) C. parapsilosis isolates have been reported in various countries but are rare.
View Article and Find Full Text PDFFever is a common presentation to urgent-care services and is linked to multiple disease processes. To rapidly determine the etiology of fever, improved diagnostic modalities are necessary. This prospective study of 100 hospitalized febrile patients included both positive (FP) and negative (FN) subjects in terms of infection status and 22 healthy controls (HC).
View Article and Find Full Text PDFNeutrophils are a vital component of the innate immune system and play an essential function in the recognition and clearance of bacterial and fungal pathogens. There is great interest in understanding mechanisms of neutrophil dysfunction in the setting of disease and deciphering potential side effects of immunomodulatory drugs on neutrophil function. We developed a high throughput flow cytometry-based assay for detecting changes to four canonical neutrophil functions following biological or chemical triggers.
View Article and Find Full Text PDFAspergillus fumigatus is a ubiquitous environmental mold that causes significant mortality particularly among immunocompromised patients. The detection of the -derived carbohydrate galactomannan in patient serum and bronchoalveolar lavage fluid is the major biomarker used to detect A. fumigatus infection in clinical medicine.
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