An altered natural killer cell immunophenotype characterizes clinically severe pediatric RSV infection.

Respiratory syncytial virus (RSV) infects nearly all children by 2 years of age and is a leading cause of pediatric hospitalizations. A subset of children with RSV infection (RSV children) develop respiratory failure requiring intensive care, but immune mechanisms distinguishing severe pediatric RSV infection are not fully elucidated. Natural killer (NK) cells are key innate immune effectors of viral host defense.

15-epi-lipoxin A promotes neutrophil exit from exudates for clearance by splenic macrophages.

Specialized proresolving mediators (SPMs) promote local macrophage efferocytosis but excess leukocytes early in inflammation require additional leukocyte clearance mechanism for resolution. Here, neutrophil clearance mechanisms from localized acute inflammation were investigated in mouse dorsal air pouches. 15-HEPE (15-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid) levels were increased in the exudates.

Pediatric Respiratory Syncytial Virus Hospitalizations and Respiratory Support After the COVID-19 Pandemic.

Importance: After the COVID-19 pandemic, there was a surge of pediatric respiratory syncytial virus (RSV) infections, but national data on hospitalization and intensive care unit use and advanced respiratory support modalities have not been reported.

Objective: To analyze demographics, respiratory support modes, and clinical outcomes of children with RSV infections at tertiary pediatric hospitals from 2017 to 2023.

Design, Setting, And Participants: This cross-sectional study evaluated children from 48 freestanding US children's hospitals registered in the Pediatric Health Information System (PHIS) database.

Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1.

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.

The Maresin 1-LGR6 axis decreases respiratory syncytial virus-induced lung inflammation.

The resolution of infection is an active process with specific molecular and cellular mechanisms that temper inflammation and enhance pathogen clearance. Here, the specialized pro-resolving mediator (SPM) Maresin 1 (MaR1) inhibited respiratory syncytial virus (RSV)-induced inflammation. inlerleukin-13 production from type 2 innate lymphoid cells (ILC) and CD4 T helper type 2 cells was decreased by exogenous MaR1.

Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization.

Lipid phosphate phosphatases are a family of enzymes with diverse cellular metabolic functions. Phospholipid phosphatase 6 (PLPP6) is a regulator of cellular polyisoprenyl phosphates; however, its functions remain to be determined. Here, mouse PLPP6 was characterized to possess similar catalytic properties as the human enzyme.

Specialized pro-resolving mediators in respiratory diseases.

Purpose Of Review: Persistent unresolved inflammation results in a number of pathologic respiratory diseases including asthma, cystic fibrosis, acute respiratory distress syndrome (ARDS) and coronavirus disease 2019 (COVID-19)-associated ARDS. Inflammation resolution is an active series of biologic processes orchestrated by a family of bioactive specialized pro-resolving mediators (SPMs) derived from essential omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). In this review, we highlight recent findings on dysregulated inflammation resolution in common respiratory diseases and recent literature on SPM generation with PUFA dietary supplementation with relevance to diseases of respiratory inflammation.

Inflammation resolution circuits are uncoupled in acute sepsis and correlate with clinical severity.

Sepsis is a critical illness characterized by dysregulated inflammatory responses lacking counter-regulation. Specialized proresolving mediators are agonists for antiinflammation and for promoting resolution, and they are protective in preclinical sepsis models. Here, in human sepsis, we mapped resolution circuits for the specialized proresolving mediators resolvin D1 and resolvin D2 in peripheral blood neutrophils and monocytes, their regulation of leukocyte activation and function ex vivo, and their relationships to measures of clinical severity.

Invasive and noninvasive ventilation strategies for acute respiratory failure in children with coronavirus disease 2019.

Purpose Of Review: Severe Acute Respiratory Syndrome Coronavirus 2 presents as symptomatic coronavirus disease 2019 (COVID-19) disease in susceptible patients. Severe pediatric COVID-19 disease is rare, limiting potential data accumulation on associated respiratory failure in children. Pediatric intensivists and pulmonologists managing COVID-19 patients look to adult guidelines and pediatric-specific consensus statements to guide management.

Human NK Cell Cytoskeletal Dynamics and Cytotoxicity Are Regulated by LIM Kinase.

NK cells provide immune surveillance and host protection against viruses and tumors through their cytotoxic effector function. Cytoskeletal rearrangement is necessary for NK cell lytic granule trafficking and immune synapse formation to trigger apoptosis of targeted cells. LIM kinase (LIMK) regulates F-actin remodeling by phosphorylating cofilin to inhibit actin severing and depolymerization.

Non-type 2 inflammation in severe asthma is propelled by neutrophil cytoplasts and maintained by defective resolution.

Asthma is a highly prevalent heterogeneous inflammatory disorder of the airways. Not all patients respond to anti-inflammatory treatment with corticosteroids, leading to significant morbidity in severe asthma. Much attention has been paid to defining the cellular and molecular mechanisms of type 2 inflammation that are operative in asthma.

Neutrophil cytoplasts induce T17 differentiation and skew inflammation toward neutrophilia in severe asthma.

Severe asthma is a debilitating and treatment refractory disease. As many as half of these patients have complex neutrophil-predominant lung inflammation that is distinct from milder asthma with type 2 eosinophilic inflammation. New insights into severe asthma pathogenesis are needed.

ALX receptor ligands define a biochemical endotype for severe asthma.

Background: In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA).

Bronchoprotective mechanisms for specialized pro-resolving mediators in the resolution of lung inflammation.

Bronchi are exposed daily to irritants, microbes and allergens as well as extremes of temperature and acid. The airway mucosal epithelium plays a pivotal role as a sentinel, releasing alarmins when danger is encountered. To maintain homeostasis, an elaborate counter-regulatory network of signals and cellular effector mechanisms are needed.

DHA- and EPA-derived resolvins, protectins, and maresins in airway inflammation.

Essential fatty acids can serve as important regulators of inflammation. A new window into mechanisms for the resolution of inflammation was opened with the identification and structural elucidation of mediators derived from these fatty acids with pro-resolving capacity. Inflammation is necessary to ensure the continued health of the organism after an insult or injury; however, unrestrained inflammation can lead to injury "from within" and chronic changes that may prove both morbid and fatal.

Pulmonary hypertension associated with scurvy and vitamin deficiencies in an autistic child.

Restricted dietary intake is common among children with behavioral issues. Here we report a case of a severely autistic child who presented initially with limp but who soon developed cough, tachypnea, hypoxia, and tachycardia. An echocardiogram revealed evidence of pulmonary hypertension (PH) with severely dilated right ventricle and elevated right-sided pressures.

Effects of cryopreservation on CD4+ CD25+ T cells of HIV-1 infected individuals.

The role of T regulatory cells (Tregs) in human immunodeficiency virus (HIV)-1 infection, although not entirely clear, has recently been highlighted. Despite their lack of specificity, fluorochrome-labeled CD4 and CD25 antibodies are common flow cytometric reagents used to identify these cells with immunosuppressive potential. Cryopreservation has previously been shown to alter the proportions of lymphocytes with certain phenotypes expressed in peripheral blood mononuclear cells (PBMCs).

Polyfunctional T cell responses are a hallmark of HIV-2 infection.

HIV-2 is distinguished clinically and immunologically from HIV-1 infection by delayed disease progression and maintenance of HIV-specific CD4(+) T cell help in most infected subjects. Thus, HIV-2 provides a unique natural human model in which to investigate correlates of immune protection against HIV disease progression. Here, we report a detailed assessment of the HIV-2-specific CD4(+) and CD8(+) T cell response compared to HIV-1, using polychromatic flow cytometry to assess the quality of the HIV-specific T cell response by measuring IFN-gamma, IL-2, TNF-alpha, MIP-1beta, and CD107a mobilization (degranulation) simultaneously following Gag peptide stimulation.

Dendritic cells are less susceptible to human immunodeficiency virus type 2 (HIV-2) infection than to HIV-1 infection.

Human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) has been documented in vivo and may be an important contributor to HIV-1 transmission and pathogenesis. HIV-1-specific CD4(+) T cells respond to HIV antigens presented by HIV-1-infected DCs and in this process become infected, thereby providing a mechanism through which HIV-1-specific CD4(+) T cells could become preferentially infected in vivo. HIV-2 disease is attenuated with respect to HIV-1 disease, and host immune responses are thought to be contributory.