GM-CSF: Orchestrating the Pulmonary Response to Infection

This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a critical role in restoring homeostasis under pathologic conditions, including infection. Given the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global spread of coronavirus disease 2019 (COVID-19), with subsequent acute respiratory distress syndrome, understanding basic lung physiology in infectious diseases is especially warranted. This review summarizes clinical and preclinical data for GM-CSF in respiratory infections, and the rationale for sargramostim (yeast-derived recombinant human [rhu] GM-CSF) as adjunctive treatment for COVID-19 and other pulmonary infectious diseases.

Training associated alterations in equine respiratory immunity using a multiomics comparative approach

Neutrophilic airway inflammation is highly prevalent in racehorses in training, with the term mild to moderate equine asthma (MMEA) being applied to the majority of such cases. Our proposed study is largely derived from the strong association between MMEA in racehorses and their entry into a race training program. The objectives of this study are to characterise the effect of training on the local pulmonary immune system by defining the gene and protein expression of tracheal wash (TW) derived samples from Thoroughbred racehorses prior to and following commencement of race training. Multiomics analysis detected 2138 differentially expressed genes and 260 proteins during the training period. Gene and protein sets were enriched for biological processes related to acute phase response, oxidative stress, haemopoietic processes, as well as to immune response and inflammation. This study demonstrated TW samples to represent a rich source of airway cells, protein and RNA to study airway immunity in the horse and highlighted the benefits of a multiomics methodological approach to studying the dynamics of equine airway immunity. Findings likely reflect the known associations between race-training and both airway inflammation and bleeding, offering further insight into the potential mechanisms which underpin training associated airway inflammation.

The Role of Innate Lymphoid Cells in Chronic Respiratory Diseases

The lung is a vital mucosal organ that is constantly exposed to the external environment, and as such, its defenses are continuously under threat. The pulmonary immune system has evolved to sense and respond to these danger signals while remaining silent to innocuous aeroantigens. The origin of the defense system is the respiratory epithelium, which responds rapidly to insults by the production of an array of mediators that initiate protection by directly killing microbes, activating tissue-resident immune cells and recruiting leukocytes from the blood. At the steady-state, the lung comprises a large collection of leukocytes, amongst which are specialized cells of lymphoid origin known as innate lymphoid cells (ILCs). ILCs are divided into three major helper-like subsets, ILC1, ILC2 and ILC3, which are considered the innate counterparts of type 1, 2 and 17 T helper cells, respectively, in addition to natural killer cells and lymphoid tissue inducer cells. Although ILCs represent a small fraction of the pulmonary immune system, they play an important role in early responses to pathogens and facilitate the acquisition of adaptive immunity. However, it is now also emerging that these cells are active participants in the development of chronic lung diseases. In this mini-review, we provide an update on our current understanding of the role of ILCs and their regulation in the lung. We summarise how these cells and their mediators initiate, sustain and potentially control pulmonary inflammation, and their contribution to the respiratory diseases chronic obstructive pulmonary disease (COPD) and asthma.

Bronchus-Associated Lymphoid Tissue (BALT) Histology and Its Role in Various Pathologies

The lower respiratory tract is in direct communication with the external environment for gas exchange to occur. Therefore, it is constantly exposed to allergens, antigens, bacteria, viruses, and a wide variety of airborne foreign bodies. Bronchus-associated lymphoid tissue (BALT), which develops in response to these exposures and is one of the most prominent representatives of mucosa-associated lymphoid tissue (MALT), is important for generating rapid and specific bronchopulmonary adaptive immune responses. Therefore, this chapter focuses on the lymphoid architecture of BALT, which was first discovered in the bronchial wall of rabbits, its inducible form called inducible BALT (iBALT), its immunological response mechanisms, and its roles in certain pathologies including infectious and autoimmune diseases as well as in allergic and malignant conditions. In conclusion, it is hypothesized that BALT plays an important role in maintaining health and in the development of lower respiratory tract diseases; thanks to the pulmonary immune system in which it functions as a functional lymphoid tissue.

Training Associated Alterations in Equine Respiratory Immunity Using a Multiomics Comparative Approach

Neutrophilic airway inflammation is highly prevalent in racehorses in training, with the term mild to moderate equine asthma (MMEA) being applied to the majority of such cases. Our proposed study is largely derived from the strong association between MMEA in racehorses and their entry into a race training program. The objectives of this study are to characterise the effect of training on the local pulmonary immune system by defining the gene and protein expression of tracheal wash (TW) derived samples from Thoroughbred racehorses prior to and following commencement of race training. Multiomics analysis detected 2,138 differentially expressed genes and 260 proteins during the training period. Gene and protein sets were enriched for biological processes related to acute phase response, oxidative stress, haemopoietic processes, as well as to immune response and inflammation. This study demonstrated TW samples to represent a rich source of airway cells, protein and RNA to study airway immunity in the horse and highlighted the benefits of a multiomics methodological approach to studying the dynamics of equine airway immunity. Findings likely reflect the known associations between race-training and both airway inflammation and bleeding, offering further insight into the potential mechanisms which underpin training associated airway inflammation.

Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection

The pulmonary immune system consists of a network of tissue-resident cells as well as immune cells that are recruited to the lungs during infection and/or inflammation. How these immune components communicate during an acute poxvirus infection is not well understood. Intranasal infection of mice with vaccinia virus causes lethal pneumonia and systemic dissemination. Here we provide evidence that type II alveolar epithelial cells (AECIIs) function as the sentinels of pulmonary infection of vaccinia virus by inducing IFN-β and IFN-stimulated genes via the activation of the MDA5 and STING-mediated nucleic acid-sensing pathways and the type I IFN positive feedback loop. This leads to the recruitment and activation of CCR2+ inflammatory monocytes in the infected lungs and their differentiation into Lyve1- interstitial macrophages (Lyve1- IMs), which efficiently engulf viral particles and block viral replication. Our results provide novel insights into how innate immune-sensing of viral infection by lung AECIIs influences the activation and differentiation of CCR2+ inflammatory monocytes to defend pulmonary poxvirus infection.

Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against an acute vaccinia infection in the lungs

SUMMARYThe pulmonary immune system consists of a network of tissue-resident cells as well as immune cells that are recruited to the lungs during infection and/or inflammation. How the two immune components cross-talk during an acute viral infection is not well understood. Intranasal infection of mice with vaccinia virus causes lethal pneumonia and systemic dissemination. Here we report that vaccinia host range protein C7 is a critical virulence factor. Vaccinia virus with deletion of C7 (VACVΔC7L) is non-pathogenic in wild-type C57BL/6J mice, but it gains virulence in mice lacking STAT2, or IFNAR1, or MDA5/STING. We provide evidence that lung type II alveolar epithelial cells (AECs) provide first-line of defense against VACVΔC7L infection by inducing IFN-β and IFN-stimulated genes via the activation of the MDA5 and STING-mediated nucleic acid-sensing pathways. This leads to recruitment of CCR2+ inflammatory monocytes into the lungs to fight against viral dissemination.

Aspergilloma pada Tuberkulosis Paru

The incidence of lung aspergillosis increases year to year. Lung aspergilloma is the most recognizable form of aspergillosis. Since 1980, the most common condition for initiating aspergillosis is tuberculosis (TB). Untreated pulmonary TB can cause several complications, such as decreases of pulmonary function, persistent pulmonary symptoms and Chronic Pulmonary Aspergillosis (CPA). More than 90% Aspergillosis is caused by Aspergillus fumigatus, this type is also widely found in people with TB. This type of fungus has a simple biological cycle with high sporulation capacity, which causes the release of conidia into the atmosphere with high concentrations. Humans inhale hundreds of conidia each day. Immuno competent hosts are capable of destroying conidia with the pulmonary immune system. Aspergillus infections cause illness when the host response is too strong or weak to the aspergillus antigen. The CPA morbidity rate is quite large with systemic symptoms and respiratory symptoms due to progressive pulmonary fibrosis and diminished lung function. During treatment, the CPA has a fatality rate of 20-33% in the short term and more than 50% in the span of 5 years. The Research Committee of the British Tuberculosis Association found that patients with post-TB cavity had a high risk of fungal colonization. The cavity formed in pulmonary TB is a suitable place for the development of various organisms including the fungus because it contains enough oxygen and necrotic tissue. The most common form of CPA associated with TB is Aspergilloma. In this review we will focus on aspergilloma, its diagnosis and management.