Neutrophils in cancer: from biology to therapy.

The view of neutrophils has shifted from simple phagocytic cells, whose main function is to kill pathogens, to very complex cells that are also involved in immune regulation and tissue repair. These cells are essential for maintaining and regaining tissue homeostasis. Neutrophils can be viewed as double-edged swords in a range of situations.

Limited impact of traumatic brain injury on the post-traumatic inflammatory cellular response.

Purpose: Trauma triggers a systemic inflammatory cellular response due to tissue damage, potentially leading to a secondary immune deficiency. Trauma severity is quantified by the Injury Severity Score (ISS). Severe Traumatic Brain Injury (TBI) is associated with high ISSs due to high lethality, despite limited tissue damage.

Automated, Point-of-Care mobile flow cytometry: Bringing the laboratory to the sample.

Background: Innate effector cells are very responsive to infectious and inflammatory cues found in damaged and inflamed tissues. Their activation is a potential target to assess the state of the immune system. Unfortunately, these cells are very susceptible for ex-vivo activation, hampering accurate interpretation of flow cytometry data.

Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors.

Precise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66bCD10CD16CD11b PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments.

Point-of-care neutrophil and monocyte surface markers differentiate bacterial from viral infections at the emergency department within 30 min.

Rapid discrimination between viral and bacterial infections in a point-of-care setting will improve clinical outcome. Expression of CD64 on neutrophils (neuCD64) increases during bacterial infections, whereas expression of CD169 on classical monocytes (cmCD169) increases during viral infections. The diagnostic value of automated point-of-care neuCD64 and cmCD169 analysis was assessed for detecting bacterial and viral infections at the emergency department.

Identification of neutrophil phenotype categories in geriatric hip fracture patients aids in personalized medicine.

Objectives: The number of geriatric hip fracture patients is high and expected to rise in the coming years, and many are frail and at risk for adverse outcomes. Early identification of high-risk patients is crucial to balance treatment and optimize outcome, but remains challenging. Previous research in patients with multitrauma suggested that neutrophil phenotype analysis could aid in early identification of high-risk patients.

Eosinophils-from cradle to grave: An EAACI task force paper on new molecular insights and clinical functions of eosinophils and the clinical effects of targeted eosinophil depletion.

Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti-inflammatory, regulatory).

Point-of-care neutrophil CD64 as a rule in diagnostic test for bacterial infections in the emergency department.

Introduction: Bacterial infections are frequently seen in the emergency department (ED), but can be difficult to distinguish from viral infections and some non-infectious diseases. Common biomarkers such as c-reactive protein (CRP) and white blood cell (WBC) counts fail to aid in the differential diagnosis. Neutrophil CD64 (nCD64), an IgG receptor, is suggested to be more specific for bacterial infections.

Quality over quantity; eosinophil activation status will deepen the insight into eosinophilic diseases.

Eosinophil associated diseases have gained much attention recently because of the introduction of specific eosinophil targeted therapies. These diseases range from acute parasitic infections to chronic inflammatory diseases such as eosinophilic asthma. In eosinophilic asthma an increased eosinophil cell count in peripheral blood is the gold standard for determination of the pheno-/endotype and severity of disease.

Visualization of the inflammatory response to injury by neutrophil phenotype categories : Neutrophil phenotypes after trauma.

Purpose: The risk of infectious complications after trauma is determined by the amount of injury-related tissue damage and the resulting inflammatory response. Recently, it became possible to measure the neutrophil phenotype in a point-of-care setting. The primary goal of this study was to investigate if immunophenotype categories based on visual recognition of neutrophil subsets are applicable to interpret the inflammatory response to trauma.

Human neutrophil kinetics: a call to revisit old evidence.

The half-life of human neutrophils is still controversial, with estimates ranging from 7-9 h to 3.75 days. This debate should be settled to understand neutrophil production in the bone marrow (BM) and the potential and limitations of emergency neutropoiesis following infection or trauma.

Longitudinal assessment of the inflammatory response: The next step in personalized medicine after severe trauma.

Infections in trauma patients are an increasing and substantial cause of morbidity, contributing to a mortality rate of 5-8% after trauma. With increased early survival rates, up to 30-50% of multitrauma patients develop an infectious complication. Trauma leads to a complex inflammatory cascade, in which neutrophils play a key role.

Neutrophil and Eosinophil Responses Remain Abnormal for Several Months in Primary Care Patients With COVID-19 Disease.

Introduction: Neutrophil and eosinophil activation and its relation to disease severity has been understudied in primary care patients with COVID-19. In this study, we investigated whether the neutrophil and eosinophil compartment were affected in primary care patients with COVID-19.

Methods: COVID-19 patients, aged ≥ 40 years with cardiovascular comorbidity presenting to the general practitioner with substantial symptoms, partaking in the COVIDSat@Home study between January and April 2021, were included.

Shift of Neutrophils From Blood to Bone Marrow Upon Extensive Experimental Trauma Surgery.

Introduction: Extensive trauma surgery evokes an immediate cellular immune response including altered circulatory neutrophil numbers. The concurrent bone marrow (BM) response however is currently unclear. We hypothesize that these BM changes include (1) a relative reduction of the bone marrow neutrophil fraction and (2) increasing heterogeneity of the bone marrow neutrophil pool due to (3) the appearance of aged/returning neutrophils from circulation into the BM-compartment.

The journey of neutropoiesis: how complex landscapes in bone marrow guide continuous neutrophil lineage determination.

Neutrophils are the most abundant white blood cell, and they differentiate in homeostasis in the bone marrow from hematopoietic stem cells (HSCs) via multiple intermediate progenitor cells into mature cells that enter the circulation. Recent findings support a continuous model of differentiation in the bone marrow of heterogeneous HSCs and progenitor populations. Cell fate decisions at the levels of proliferation and differentiation are enforced through expression of lineage-determining transcription factors and their interactions, which are influenced by intrinsic (intracellular) and extrinsic (extracellular) mechanisms.

Three encephalitis-causing amoebae and their distinct interactions with the host.

Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba spp. can cause devastating brain infections in humans which almost always result in death. The symptoms of the three infections overlap, but brain inflammation and the course of the disease differ, depending on the amoeba that is responsible.

Repetitive Immune-Mediated Noninfectious Endocarditis Necessitating 5 Mitral Valve Replacements.

We present a young patient who had to undergo 5 mitral valve replacements (MVR) because of a repetitive immune-mediated noninfectious endocarditis. The patient was treated with multiple anti-inflammatory drugs and high-dose prednisone. After the fifth MVR, the patient remained in stable condition using Anakinra after 22 months of follow-up.

Serum Biomarker Profile Including CCL1, CXCL10, VEGF, and Adenosine Deaminase Activity Distinguishes Active From Remotely Acquired Latent Tuberculosis.

Introduction: There is an urgent medical need to differentiate active tuberculosis (ATB) from latent tuberculosis infection (LTBI) and prevent undertreatment and overtreatment. The aim of this study was to identify biomarker profiles that may support the differentiation between ATB and LTBI and to validate these signatures.

Materials And Methods: The discovery cohort included adult individuals classified in four groups: ATB (n = 20), LTBI without prophylaxis (untreated LTBI; n = 20), LTBI after completion of prophylaxis (treated LTBI; n = 20), and healthy controls (HC; n = 20).

Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma.

Mepolizumab (anti-IL-5) is a successful biological for treatment of T2/eosinophilic asthma by blocking the IL-5-eosinophil axis. The kinetics of human eosinophils in blood and sputum was determined to better understand the underlying mechanism(s). Pulse-chase labeling was performed with 6,6-H-glucose in patients with asthma after short term (4 days) and long term (84 days) treatment with mepolizumab (n = 10) or placebo (n = 10).

Transformation of multicolour flow cytometry data with OTflow prevents misleading multivariate analysis results and incorrect immunological conclusions.

The rapid evolution of the flow cytometry field, currently allowing the measurement of 30-50 parameters per cell, has led to a marked increase in deep multivariate information. Manual gating is insufficient to extract all this information. Therefore, multivariate analysis (MVA) methods have been developed to extract information and efficiently analyze the high-density multicolour flow cytometry (MFC) data.

Kinetics of Neutrophil Subsets in Acute, Subacute, and Chronic Inflammation.

At homeostasis the vast majority of neutrophils in the circulation expresses CD16 and CD62L within a narrow expression range, but this quickly changes in disease. Little is known regarding the changes in kinetics of neutrophils phenotypes in inflammatory conditions. During acute inflammation more heterogeneity was found, characterized by an increase in CD16 banded neutrophils.