Eosinophils as modulators of host defense during parasitic, fungal, bacterial, and viral infections.

Eosinophils, traditionally associated as central innate effector cells with type 2 immunity during allergic and helminth parasitic diseases, have recently been revealed to have important roles in tissue homeostasis as well as host defense in a broader variety of infectious diseases. In a dedicated session at the 2023 biennial conference of the International Eosinophil Society titled "Eosinophils in Host Defense," the multifaceted roles eosinophils play against diverse pathogens, ranging from parasites to fungi, bacteria, and viruses, were presented. In this review, the session speakers offer a comprehensive summary of recent discoveries across pathogen classes, positioning eosinophils as pivotal leukocytes in both host defense and pathology.

Postinfectious Pulmonary Complications: Establishing Research Priorities to Advance the Field: An Official American Thoracic Society Workshop Report.

Continued improvements in the treatment of pulmonary infections have paradoxically resulted in a growing challenge of individuals with postinfectious pulmonary complications (PIPCs). PIPCs have been long recognized after tuberculosis, but recent experiences such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have underscored the importance of PIPCs following other lower respiratory tract infections. Independent of the causative pathogen, most available studies of pulmonary infections focus on short-term outcomes rather than long-term morbidity among survivors.

Host mitochondria: more than an organelle in SARS-CoV-2 infection.

Since December 2019, the world has been facing viral pandemic called COVID-19 (Coronavirus disease 2019) caused by a new beta-coronavirus named severe acute respiratory syndrome coronavirus-2, or SARS-CoV-2. COVID-19 patients may present with a wide range of symptoms, from asymptomatic to requiring intensive care support. The severe form of COVID-19 is often marked by an altered immune response and cytokine storm.

Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants.

The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, yet we have limited information regarding the breadth of variant-specific host responses. Using primary cell cultures and the K18-hACE2 mouse, we investigated the replication, innate immune response, and pathology of closely related, clinical variants circulating during the first wave of the pandemic.

Human matters in asthma: Considering the microbiome in pulmonary health.

Microbial communities form an important symbiotic ecosystem within humans and have direct effects on health and well-being. Numerous exogenous factors including airborne triggers, diet, and drugs impact these established, but fragile communities across the human lifespan. Crosstalk between the mucosal microbiota and the immune system as well as the gut-lung axis have direct correlations to immune bias that may promote chronic diseases like asthma.

Impact of Therapeutics on Unified Immunity During Allergic Asthma and Respiratory Infections.

Asthma is a common chronic respiratory disease that affects millions of people worldwide. Patients with allergic asthma, the most prevalent asthma endotype, are widely considered to possess a defective immune response against some respiratory infectious agents, including viruses, bacteria and fungi. Furthermore, respiratory pathogens are associated with asthma development and exacerbations.

Initiation and Pathogenesis of Severe Asthma with Fungal Sensitization.

Fungi represent one of the most diverse and abundant eukaryotes on earth, and their ubiquity and small proteolytically active products make them pervasive allergens that affect humans and other mammals. The immunologic parameters surrounding fungal allergies are still not fully elucidated despite their importance given that a large proportion of severe asthmatics are sensitized to fungal allergens. Herein, we explore fungal allergic asthma with emphasis on mouse models that recapitulate the characteristics of human disease, and the main leukocyte players in the pathogenesis of fungal allergies.

Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza A Virus Infection in C57BL/6 Mice.

Eosinophils, previously considered terminally differentiated effector cells, have multifaceted functions in tissues. We previously found that allergic mice with eosinophil-rich inflammation were protected from severe influenza and discovered specialized antiviral effector functions for eosinophils including promoting cellular immunity during influenza. In this study, we hypothesized that eosinophil responses during the early phase of influenza contribute to host protection.

Murine Models of Eosinophil Function in Fungal and Viral Infections.

Eosinophils are granulocytes that were historically considered to be terminally differentiated at the time of bone marrow egress. However, more recent evidence provides a new outlook on these cells as complex immunomodulators that are involved in host defense and homeostasis. Our work established a role for eosinophils as mediators of antiviral immune responses during influenza in hosts that were sensitized and challenged with fungal allergens.

Questioning Cause and Effect: Children with Severe Asthma Exhibit High Levels of Inflammatory Biomarkers Including Beta-Hexosaminidase, but Low Levels of Vitamin A and Immunoglobulins.

Asthma affects over 8% of the pediatric population in the United States, and Memphis, Tennessee has been labeled an asthma capital. Plasma samples were analyzed for biomarker profiles from 95 children with severe asthma and 47 age-matched, hospitalized nonasthmatic controls at Le Bonheur Children's Hospital in Memphis, where over 4000 asthmatics are cared for annually. Asthmatics exhibited significantly higher levels of periostin, surfactant protein D, receptor for advanced glycation end products and β-hexosaminidase compared to controls.

Influenza A virus directly modulates mouse eosinophil responses.

Allergic asthma and influenza are common respiratory diseases with a high probability of co-occurrence. During the 2009 influenza pandemic, hospitalized patients with influenza experienced lower morbidity if asthma was an underlying condition. We have previously demonstrated that acute allergic asthma protects mice from severe influenza and have implicated eosinophils in the airways of mice with allergic asthma as participants in the antiviral response.

Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and .

The primary function of the respiratory system of gas exchange renders it vulnerable to environmental pathogens that circulate in the air. Physical and cellular barriers of the respiratory tract mucosal surface utilize a variety of strategies to obstruct microbe entry. Physical barrier defenses including the surface fluid replete with antimicrobials, neutralizing immunoglobulins, mucus, and the epithelial cell layer with rapidly beating cilia form a near impenetrable wall that separates the external environment from the internal soft tissue of the host.

Convergence of Inflammatory Pathways in Allergic Asthma and Sickle Cell Disease.

The underlying pathologies of sickle cell disease and asthma share many characteristics in terms of respiratory inflammation. The principal mechanisms of pulmonary inflammation are largely distinct, but activation of common pathways downstream of the initial inflammatory triggers may lead to exacerbation of both disease states. The altered inflammatory landscape of these respiratory pathologies can differentially impact respiratory pathogen susceptibility in patients with sickle cell disease and asthma.

Allergic inflammation alters the lung microbiome and hinders synergistic co-infection with H1N1 influenza virus and Streptococcus pneumoniae in C57BL/6 mice.

Asthma is a chronic airways condition that can be exacerbated during respiratory infections. Our previous work, together with epidemiologic findings that asthmatics were less likely to suffer from severe influenza during the 2009 pandemic, suggest that additional complications of influenza such as increased susceptibility to bacterial superinfection, may be mitigated in allergic hosts. To test this hypothesis, we developed a murine model of 'triple-disease' in which mice rendered allergic to Aspergillus fumigatus were co-infected with influenza A virus and Streptococcus pneumoniae seven days apart.

The Role of Innate Leukocytes during Influenza Virus Infection.

Influenza virus infection is a serious threat to humans and animals, with the potential to cause severe pneumonia and death. Annual vaccination strategies are a mainstay to prevent complications related to influenza. However, protection from the emerging subtypes of influenza A viruses (IAV) even in vaccinated individuals is challenging.

Eosinophils: Nemeses of Pulmonary Pathogens?

Purpose Of Review: Eosinophils are short-lived granulocytes that contain a variety of proteins and lipids traditionally associated with host defense against parasites. The primary goal of this review is to examine more recent evidence that challenged this rather outdated role of eosinophils in the context of pulmonary infections with helminths, viruses, and bacteria.

Recent Findings: While eosinophil mechanisms that counter parasites, viruses, and bacteria are similar, the kinetics and impact may differ by pathogen type.

Macrophage CD14 impacts immune defenses against influenza virus in allergic hosts.

Asthma and influenza are leading causes of worldwide morbidity and mortality. Although these two conditions can co-exist in the same patient, the immune parameters that impact disease outcomes are not fully elucidated. The importance of macrophages to both conditions suggested a role for CD14, a co-receptor for endotoxin, as a regulatory mechanism for innate immune responses during asthma and influenza co-morbidity.

Influenza in Asthmatics: For Better or for Worse?

Asthma and influenza are two pathologic conditions of the respiratory tract that affect millions worldwide. Influenza virus of the 2009 pandemic was highly transmissible and caused severe respiratory disease in young and middle-aged individuals. Asthma was discovered to be an underlying co-morbidity that led to hospitalizations during this influenza pandemic albeit with less severe outcomes.

Tannic Acid-Lung Fluid Assemblies Promote Interaction and Delivery of Drugs to Lung Cancer Cells.

Lung cancer (LC) is one of the leading causes of death in both men and women in the United States. Tannic acid (TA), a water-soluble polyphenol, exhibits a wide range of biological activities. TA has received much attention as a promising compound in the biomaterial and drug delivery fields.

Chronic features of allergic asthma are enhanced in the absence of resistin-like molecule-beta.

Asthma is characterized by inflammation and architectural changes in the lungs. A number of immune cells and mediators are recognized as initiators of asthma, although therapeutics based on these are not always effective. The multifaceted nature of this syndrome necessitate continued exploration of immunomodulators that may play a role in pathogenesis.

-Derived Mannan Does Not Alter Immune Responses to Allergens.

Severe asthma with fungal sensitization predominates in the population suffering from allergic asthma, to which there is no cure. While corticosteroids are the mainstay in current treatment, other means of controlling inflammation may be beneficial. Herein, we hypothesized that mannan from would dampen the characteristics of fungal allergic asthma by altering the pulmonary immune responses.

Understanding fibrosis in eosinophilic esophagitis: Are we there yet?

Eosinophilic esophagitis (EoE) is an immune/antigen-mediated, progressive fibrostenotic disease characterized by symptoms of esophageal dysfunction and abnormal eosinophilic infiltration in the esophagus. Despite current treatment modalities of dietary antigen elimination or topical corticosteroids, a subset of patients do not have clinical or histologic response. Even with resolution of superficial epithelial eosinophilia, patients may still have progressive subepithelial fibrosis, which may lead to esophageal strictures over time.

Humoral immune responses during asthma and influenza co-morbidity in mice.

Humoral immunity serve dual functions of direct pathogen neutralization and enhancement of leukocyte function. Antibody classes are determined by antigen triggers, and the resulting antibodies can contribute to disease pathogenesis and host defense. Although asthma and influenza are immunologically distinct diseases, since we have found that allergic asthma exacerbation promotes antiviral host responses to influenza A virus, we hypothesized that humoral immunity may contribute to allergic host protection during influenza.