Pulmonary Defense Research Articles

Cryptococcus neoformans trehalose-6-phosphate synthase (tps1) promotes organ-specific virulence and fungal protection against multiple lines of host defenses.

Trehalose-6-phosphate synthase (TPS1) was identified as a virulence factor for Cryptococcus neoformans and a promising therapeutic target. This study reveals previously unknown roles of TPS1 in evasion of host defenses during pulmonary and disseminated phases of infection. In the pulmonary infection model, TPS1-deleted (tps1Δ) Cryptococci are rapidly cleared by mouse lungs whereas TPS1-sufficent WT (H99) and revertant (tps1Δ:TPS1) strains expand in the lungs and disseminate, causing 100% mortality. Rapid pulmonary clearance of tps1Δ mutant is T-cell independent and relies on its susceptibility to lung resident factors and innate immune factors, exemplified by tps1Δ but not H99 inhibition in a coculture with dispersed lung cells and its rapid clearance coinciding with innate leukocyte infiltration. In the disseminated model of infection, which bypasses initial lung-fungus interactions, tps1Δ strain remains highly attenuated. Specifically, tps1Δ mutant is unable to colonize the lungs from the bloodstream or expand in spleens but is capable of crossing into the brain, where it remains controlled even in the absence of T cells. In contrast, strains H99 and tps1Δ:TPS1 rapidly expand in all studied organs, leading to rapid death of the infected mice. Since the rapid pulmonary clearance of tps1Δ mutant resembles a response to acapsular strains, the effect of tps1 deletion on capsule formation in vitro and in vivo was examined. Tps1Δ cryptococci form capsules but with a substantially reduced size. In conclusion, TPS1 is an important virulence factor, allowing C. neoformans evasion of resident pulmonary and innate defense mechanisms, most likely via its role in cryptococcal capsule formation.

Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung

Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers. Infection experiments with mice transplanted with patient fecal material reveal that these antibiotic-induced microbiota perturbations impair pulmonary defense against MDR Klebsiella pneumoniae. This is dependent on inflammatory monocytes (IMs), whose fatty acid receptor (FFAR)2/3-controlled and phagolysosome-dependent antibacterial activity is compromized in mice transplanted with antibiotic-associated patient microbiota. Collectively, we characterize how clinically relevant antibiotics affect antimicrobial defense in the context of human microbiota, and reveal a critical impairment of IM´s antimicrobial activity. Our study provides additional arguments for the rational use of antibiotics and offers mechanistic insights for the development of novel prophylactic strategies to protect high-risk patients from HAP.

Deciphering regulatory patterns in a mouse model of hyperoxia-induced acute lung injury.

Oxygen therapy plays a pivotal role in treating critically ill patients in the intensive care unit (ICU). However, excessive oxygen concentrations can precipitate hyperoxia, leading to damage in multiple organs, with a notable effect on the lungs. Hyperoxia condition may lead to hyperoxia-induced acute lung injury (HALI), deemed as a milder form of acute respiratory distress syndrome (ARDS). Given its clinical importance and practical implications, there is a compelling need to investigate the underlying pathogenesis and comprehensively understand the regulatory mechanisms implicated in the development of HALI. In this study, we conducted a mouse model with HALI and performed regulatory mechanism analysis using RNA-seq on both HALI and control group. Comprehensive analysis revealed 727 genes of significant differential expression, including 248 long non-coding RNAs (lncRNAs). Also, alternative splicing events were identified from sequencing results. Notably, we observed up-regulation or abnormal alternative splicing of genes associated with immune response and ferroptosis under hyperoxia conditions. Utilizing weighted gene co-expression network analysis (WGCNA), we ascertained that genes involved in immune response formed a distinct cluster, showcasing an up-regulated pattern in hyperoxia, consistent with previous studies. Furthermore, a competing endogenous RNA (ceRNA) network was constructed, including 78 differentially expressed mRNAs and six differentially expressed lncRNAs, including H19. These findings uncover the intricate interplay of multiple transcriptional regulatory mechanisms specifically tailored to the pulmonary defense against HALI, substantiating the importance of these non-coding RNAs in this disease context. Our results provide new insights into the potential mechanisms and underlying pathogenesis in the development of HALI at the post-transcriptional level. The findings of this study reveal potential regulatory interactions and biological roles of specific lncRNAs and genes, such as H19 and Sox9, encompassing driven gene expression patterns, alternative splicing events, and lncRNA-miRNA-mRNA ceRNA networks. These findings may pave the way for advancing therapeutic strategies and reducing the risk associated with oxygen treatment for patients.

The microbiome: an integral player in immune homeostasis and inflammation in the respiratory tract.

The last decade of microbiome research has highlighted its fundamental role in systemic immune and metabolic homeostasis. The microbiome plays a prominent role during gestation and into early life, when maternal lifestyle factors shape immune development of the newborn. Breast milk further shapes gut colonization, supporting the development of tolerance to commensal bacteria and harmless antigens while preventing outgrowth of pathogens. Environmental microbial and lifestyle factors that disrupt this process can dysregulate immune homeostasis, predisposing infants to atopic disease and childhood asthma. In health, the low-biomass lung microbiome, together with inhaled environmental microbial constituents, establishes the immunological set point that is necessary to maintain pulmonary immune defense. However, in disease perturbations to immunological and physiological processes allow the upper respiratory tract to act as a reservoir of pathogenic bacteria, which can colonize the diseased lung and cause severe inflammation. Studying these host-microbe interactions in respiratory diseases holds great promise to stratify patients for suitable treatment regimens and biomarker discovery to predict disease progression. Preclinical studies show that commensal gut microbes are in a constant flux of cell division and death, releasing microbial constituents, metabolic by-products, and vesicles that shape the immune system and can protect against respiratory diseases. The next major advances may come from testing and utilizing these microbial factors for clinical benefit and exploiting the predictive power of the microbiome by employing multiomics analysis approaches.

Acyloxyacyl hydrolase promotes pulmonary defense by preventing alveolar macrophage tolerance.

Although alveolar macrophages (AMs) play important roles in preventing and eliminating pulmonary infections, little is known about their regulation in healthy animals. Since exposure to LPS often renders cells hyporesponsive to subsequent LPS exposures ("tolerant"), we tested the hypothesis that LPS produced in the intestine reaches the lungs and stimulates AMs, rendering them tolerant. We found that resting AMs were more likely to be tolerant in mice lacking acyloxyacyl hydrolase (AOAH), the host lipase that degrades and inactivates LPS; isolated Aoah-/- AMs were less responsive to LPS stimulation and less phagocytic than were Aoah+/+ AMs. Upon innate stimulation in the airways, Aoah-/- mice had reduced epithelium- and macrophage-derived chemokine/cytokine production. Aoah-/- mice also developed greater and more prolonged loss of body weight and higher bacterial burdens after pulmonary challenge with Pseudomonas aeruginosa than did wildtype mice. We also found that bloodborne or intrarectally-administered LPS desensitized ("tolerized") AMs while antimicrobial drug treatment that reduced intestinal commensal Gram-negative bacterial abundance largely restored the innate responsiveness of Aoah-/- AMs. Confirming the role of LPS stimulation, the absence of TLR4 prevented Aoah-/- AM tolerance. We conclude that commensal LPSs may stimulate and desensitize (tolerize) alveolar macrophages in a TLR4-dependent manner and compromise pulmonary immunity. By inactivating LPS in the intestine, AOAH promotes antibacterial host defenses in the lung.

A critical assessment of the cellular defences of the avian respiratory system: are birds in general and poultry in particular relatively more susceptible to pulmonary infections/afflictions?

In commercial poultry farming, respiratory diseases cause high morbidities and mortalities, begetting colossal economic losses. Without empirical evidence, early observations led to the supposition that birds in general, and poultry in particular, have weak innate and adaptive pulmonary defences and are therefore highly susceptible to injury by pathogens. Recent findings have, however, shown that birds possess notably efficient pulmonary defences that include: (i) a structurally complex three-tiered airway arrangement with aerodynamically intricate air-flow dynamics that provide efficient filtration of inhaled air; (ii) a specialised airway mucosal lining that comprises air-filtering (ciliated) cells and various resident phagocytic cells such as surface and tissue macrophages, dendritic cells and lymphocytes; (iii) an exceptionally efficient mucociliary escalator system that efficiently removes trapped foreign agents; (iv) phagocytotic atrial and infundibular epithelial cells; (v) phagocytically competent surface macrophages that destroy pathogens and injurious particulates; (vi) pulmonary intravascular macrophages that protect the lung from the vascular side; and (vii) proficiently phagocytic pulmonary extravasated erythrocytes. Additionally, the avian respiratory system rapidly translocates phagocytic cells onto the respiratory surface, ostensibly from the subepithelial space and the circulatory system: the mobilised cells complement the surface macrophages in destroying foreign agents. Further studies are needed to determine whether the posited weak defence of the avian respiratory system is a global avian feature or is exclusive to poultry. This review argues that any inadequacies of pulmonary defences in poultry may have derived from exacting genetic manipulation(s) for traits such as rapid weight gain from efficient conversion of food into meat and eggs and the harsh environmental conditions and severe husbandry operations in modern poultry farming. To reduce pulmonary diseases and their severity, greater effort must be directed at establishment of optimal poultry housing conditions and use of more humane husbandry practices.

Comparison of the effects of electronic cigarette vapours and tobacco smoke extracts on human neutrophilsin vitro

Electronic cigarettes (ECs) are electronic aerosol delivery systems composed of nicotine and various chemicals, which are widely used to facilitate smoking cessation. Although ECs are considered safer than cigarettes, they do, however, contain chemical toxicants, some of which may interact with cells of the host's innate immune system of which neutrophils constitute a key component. The current study was designed to compare the effects of aqueous EC aerosol extracts (ECEs; with or without nicotine) with those of cigarette smoke extract (CSE) on neutrophil and platelet reactivity in vitro. Neutrophil reactivity is characterised by the generation of reactive oxygen species (ROS), degranulation (elastase release) and the release of extracellular DNA (neutrophil extracellular trap (NET) formation: NETosis), which were measured using chemiluminescence, spectrophotometric and microscopic procedures, respectively. Platelet reactivity was measured according to the magnitude of upregulated expression of the adhesion molecule CD62P on activated cells using a flow cytometric procedure. Exposure of neutrophils to either ECEs or CSE caused a significant inhibition of ROS generation and elastase release by N-formyl-l-methionyl-l-leucyl-l-phenylalanine (1 µM)-activated neutrophils. Pre-treatment of neutrophils with CSE also resulted in a marked attenuation of phorbol 12-myristate 13-acetate (6.25 nM)-mediated release of extracellular DNA, which was unaffected by the ECEs. Similarly, CSE, but not the ECEs, inhibited the expression of CD62P by platelets activated with ADP (100 µM). These observations suggest that ECE aerosols may inhibit some of the immuno-protective activities of neutrophils such as ROS production and elastase release by activated cells, the effect of which was not enhanced by inclusion of nicotine. The inhibitory effects of CSE were significantly more pronounced than those of ECEs, especially so for suppression of NET formation and platelet activation. If operative in vivo, these harmful immunosuppressive effects of ECEs may compromise intrinsic pulmonary antimicrobial defence mechanisms, albeit less so than cigarette smoke.

Updated Mineral Composition and Potential Therapeutic Properties of Different Varieties of Olive Leaves from Olea europaea.

Olea europaea L. folium has been studied for its potential nutraceutical properties. Quantitative and qualitative analyses were conducted on samples of Madural, Verdeal, and Cobrançosa elementary leaves and leave sprouts (mamões) collected in the region of Valpaços, Portugal. Mineral analysis determined the measurements of the levels of several macro- and micro-elements based on ICP-MS techniques. The inorganic analysis in this work allowed us to propose olive leaf extract (OLE) from different cultivars as a viable and affordable source of mineral substrates to address disorders related to essential elements such as Na, K, Mg, Ca, Mn, Fe, and Cu deficiencies. Given the importance of the research on novel therapies, finding a suitable substrate for extracting quality amounts of mineral is a priority. The physiological influence of enzymes dependent on minerals with regard to neuroinflammatory and neurobehavioral, metabolic, cardiovascular, osteodegenerative, anti-aging, pulmonary, and immunological defense disorders might dictate the importance of further research for designing supplementation based on the nutraceutical potential of OLE of these cultivars predominant in the northern region of Portugal.

Updated Organic Composition and Potential Therapeutic Properties of Different Varieties of Olive Leaves from Olea europaea.

Olea europaea L. folium merits further exploration of the potential of its substrates for therapeutic supplements. Quantitative and qualitative analyses were conducted on samples of Madural, Verdeal, and Cobrançosa elementary leaves and leaf sprouts (mamões) collected in the region of Valpaços, Portugal. Organic analysis assessed the moisture content, total carbohydrates, ash, protein, and fat contents, total phenolic content (TPC), vitamin E, and fatty acid (FA) profiles. Moisture content was determined through infrared hygrometry and TPC was determined by a spectrophotometric method. Concerning organic analysis, all leaf samples showed similar moisture content, though Cobrançosa's leaf sprouts and Verdeal's elementary leaves had slightly lower contents. Meanwhile, these cultivars also showed a higher TPC, α-tocopherol isomer, and fatty acid composition (FAC). FAC in all samples exhibited higher contents of PUFA and SFA than MUFA, with a predominance of linolenic and palmitic acids. Organic analyses of Cobrançosa's leaf sprouts and Verdeal's elementary leaf extracts allow for the prediction of adequate physiological properties regarding neuroinflammatory, neurobehavioral, metabolic, cardiovascular, osteo-degenerative, anti-ageing, pulmonary, and immunological defense disorders. These physiological changes observed in our preliminary in silico studies suggest an excellent nutraceutical, which should be borne in mind during severe pandemic situations.

Influenza Virus Infection Increases Host Susceptibility To Secondary Infection with Pseudomonas aeruginosa, and This Is Attributed To Neutrophil Dysfunction through Reduced Myeloperoxidase Activity.

Secondary bacterial infection greatly increased the morbidity and mortality of influenza virus infection. To investigate the underlying mechanism by which influenza impairs the pulmonary defense against secondary Pseudomonas aeruginosa ( P. aeruginosa ) infection, we established a lethal mouse model in which to study secondary P. aeruginosa infection after influenza virus infection. We found a significant increase in host susceptibility to a secondary infection with P. aeruginosa in mice after an influenza virus infection, and this was accompanied by severe immunopathology and pulmonary inflammation. Importantly, we demonstrated that neutrophils were essential for P. aeruginosa clearance in secondarily infected mice. Further, we revealed that influenza impaired the phagocytosis and digestion functions of pulmonary neutrophils for P. aeruginosa clearance. We identified that the activity of reactive oxygen species (ROS) and the myeloperoxidase (MPO) activity of neutrophils in the lungs played an important role in antibacterial host defense in influenza-infected lungs. Hereby, influenza virus infection causes deficient MPO activity in neutrophils, and this contributes to the increased susceptibility to secondary P. aeruginosa infection. Treatment with Bacillus Calmette-Guerin polysaccharide nucleic acid (BCG-PSN) prior to secondary P. aeruginosa infection may improve the function of neutrophils, resulting in significantly reduced lethality during secondary P. aeruginosa infection. We also demonstrated that treatment with anti-influenza immune serum during the early stage of an influenza virus infection could decrease the disease severity of secondary P. aeruginosa infection. Our findings suggest that improving the MPO activity of neutrophils may provide a therapeutic strategy for viral-bacterial coinfection. IMPORTANCE A secondary bacterial infection, such as that of P. aeruginosa , often occurs after a pulmonary virus infection and contributes to severe disease. However, the underlying mechanisms responsible for viral-bacterial synergy in the lung remain largely unknown. In this study, we reported that influenza virus infection increases a host’s susceptibility to secondary infection by P. aeruginosa by reducing the MPO activity of neutrophils. We also demonstrated that treatment with BCG-PSN or anti-influenza immune serum prior to secondary P. aeruginosa infection can reduce the disease severity. Our findings suggest that improving the MPO activity of neutrophils may provide a therapeutic strategy for viral-bacterial coinfection.

Pneumonia bacteriana em equinos associada à infecção por Escherichia coli: relato de cinco casos

ABSTRACT Respiratory diseases have a major impact on sport horses and are often cited as the second most common reason for loss of training days and significant veterinary costs. Adult horses most commonly develop pneumonia when bacteria aspirated from the environment, nose, or oropharynx reach the lower airways and overwhelm the pulmonary defense mechanisms. This article report five cases of bacterial pneumonia in horses associated with infection by Eschericia coli. Five Quarter horses, three males and two females, with ages varying from 5 to 12 years, were examined for diagnosis of respiratory disease characterized by apathy, cough and lack of appetite. Auscultation of the thorax revealed increased harsh breath sounds dorsally, crackles, wheezes, and dullness of respiratory sounds ventrally. Manipulation of the trachea and larynx induced cough. Culture results were positive for Escherichia coli. The therapeutic protocol consisted of anti-inflammatory, antibiotic therapy, and supportive care. Flunixin meglumine was administered intravenously at 24-hour intervals over eight days. Ceftiofur sodium was prescribed intramuscularly, q.d., for 15 days. Horses were clinically monitored daily until complete remission of clinical signs. None of the animals relapsed, and all returned to routine athletic activities.

Spinal Cord Injury Impairs Lung Immunity in Mice.

Pulmonary infection is a leading cause of morbidity and mortality after spinal cord injury (SCI). Although SCI causes atrophy and dysfunction in primary and secondary lymphoid tissues with a corresponding decrease in the number and function of circulating leukocytes, it is unknown whether this SCI-dependent systemic immune suppression also affects the unique tissue-specific antimicrobial defense mechanisms that protect the lung. In this study, we tested the hypothesis that SCI directly impairs pulmonary immunity and subsequently increases the risk for developing pneumonia. Using mouse models of severe high-level SCI, we find that recruitment of circulating leukocytes and transcriptional control of immune signaling in the lung is impaired after SCI, creating an environment that is permissive for infection. Specifically, we saw a sustained loss of pulmonary leukocytes, a loss of alveolar macrophages at chronic time points postinjury, and a decrease in immune modulatory genes, especially cytokines, needed to eliminate pulmonary infections. Importantly, this injury-dependent impairment of pulmonary antimicrobial defense is only partially overcome by boosting the recruitment of immune cells to the lung with the drug AMD3100, a Food and Drug Administration-approved drug that mobilizes leukocytes and hematopoietic stem cells from bone marrow. Collectively, these data indicate that the immune-suppressive effects of SCI extend to the lung, a unique site of mucosal immunity. Furthermore, preventing lung infection after SCI will likely require novel strategies, beyond the use of orthodox antibiotics, to reverse or block tissue-specific cellular and molecular determinants of pulmonary immune surveillance.

Transcriptomic atlas of GNAT family members in pulmonary epithelia under pathological conditions using single‐cell and bulk cell sequencing

Transcriptomic atlas of GNAT family members in pulmonary epithelia under pathological conditions using single‐cell and bulk cell sequencing

Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection

ABSTRACT Nontuberculous mycobacterial pulmonary diseases (NTM-PDs) are emerging as global health threats with issues of antibiotic resistance. Accumulating evidence suggests that the gut–lung axis may provide novel candidates for host-directed therapeutics against various infectious diseases. However, little is known about the gut–lung axis in the context of host protective immunity to identify new therapeutics for NTM-PDs. This study was performed to identify gut microbes and metabolites capable of conferring pulmonary immunity to NTM-PDs. Using metabolomics analysis of sera from NTM-PD patients and mouse models, we showed that the levels of l-arginine were decreased in sera from NTM-PD patients and NTM-infected mice. Oral administration of l-arginine significantly enhanced pulmonary antimicrobial activities with the expansion of IFN-γ-producing effector T cells and a shift to microbicidal (M1) macrophages in the lungs of NTM-PD model mice. Mice that received fecal microbiota transplants from l-arginine-treated mice showed increased protective host defense in the lungs against NTM-PD, whereas l-arginine-induced pulmonary host defense was attenuated in mice treated with antibiotics. Using 16S rRNA sequencing, we further showed that l-arginine administration resulted in enrichment of the gut microbiota composition with Bifidobacterium species. Notably, oral treatment with either Bifidobacterium pseudolongum or inosine enhanced antimicrobial pulmonary immune defense against NTM infection, even with multidrug-resistant clinical NTM strains. Our findings indicate that l-arginine-induced gut microbiota remodeling with enrichment of B. pseudolongum boosts pulmonary immune defense against NTM infection by driving the protective gut–lung axis in vivo.

The Effect of CFTR Modulators on Airway Infection in Cystic Fibrosis.

The advent of Cystic fibrosis transmembrane receptor (CFTR) modulators in 2012 was a critical event in the history of cystic fibrosis (CF) treatment. Unlike traditional therapies that target downstream effects of CFTR dysfunction, CFTR modulators aim to correct the underlying defect at the protein level. These genotype-specific therapies are now available for an increasing number of CF patients, transforming the way we view the condition from a life-limiting disease to one that can be effectively managed. Several studies have demonstrated the vast improvement CFTR modulators have on normalization of sweat chloride, CFTR function, clinical endpoints, and frequency of pulmonary exacerbation. However, their impact on other aspects of the disease, such as pathogenic burden and airway infection, remain under explored. Frequent airway infections as a result of increased susceptibility and impaired innate immune response are a serious problem within CF, often leading to accelerated decline in lung function and disease progression. Current evidence suggests that CFTR modulators are unable to eradicate pathogenic organisms in those with already established lung disease. However, this may not be the case for those with relatively low levels of disease progression and conserved microbial diversity, such as young patients. Furthermore, it remains unknown whether the restorative effects exerted by CFTR modulators extend to immune cells, such as phagocytes, which have the potential to modulate the response of people with CF (pwCF) to infection. Throughout this review, we look at the potential impact of CFTR modulators on airway infection in CF and their ability to shape impaired pulmonary defences to pathogens.

Risk of an Adverse Event in Individuals Who Aspirate: A Review of Current Literature on Host Defenses and Individual Differences.

The presence of oropharyngeal dysphagia increases the likelihood of prandial aspiration, and aspiration increases the likelihood of a dysphagia-related pulmonary sequelae such as aspiration pneumonia, acute respiratory distress syndrome, pulmonary fibrosis, and even death. Although these outcomes are unfortunate, it is important to point out that these consequences are not solely determined by the presence of aspiration. The purpose of this tutorial is to provide current information on pulmonary defenses and the variables that increase risk of an adverse outcome in individuals who aspirate. This tutorial reviews the basics of lung defenses and summarizes the literature to make the case that the host is a central theme in dysphagia management. Case studies are employed to highlight the key variables. Based on a literature review, a series of questions are proposed for consideration in dysphagia management. These questions, which take the focus away from the presence of aspiration and toward the associated risks within an individual, are then applied to two case studies. A guiding framework is proposed to encourage clinicians to assess more than the presence of aspiration and consider the individual's ability to cope with the aspirated material. In the presence of aspiration, clinicians are urged to focus on the risk factors that can lead to a negative consequence, identify which factors are modifiable, and determine when a level of risk is acceptable.

Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection.

BackgroundType III interferon, or interferon lambda (IFNλ) is a crucial antiviral cytokine induced by influenza infection. While IFNλ is important for anti-viral host defense, published data demonstrate that IFNλ is pathogenic during influenza/bacterial super-infection. It is known that polymorphisms in specific IFNλ genes affect influenza responses, but the effect of IFNλ subtypes on bacterial super-infection is unknown.MethodsUsing an established model of influenza, Staphylococcus aureus super-infection, we studied IFNλ3-/- and control mice to model a physiologically relevant reduction in IFNλ and to address its role in super-infection.ResultsSurprisingly, IFNλ3-/- mice did not have significantly lower total IFNλ than co-housed controls, and displayed no change in viral or bacterial clearance. Importantly, both control and IFNλ3-/- mice displayed a positive correlation between viral burden and total IFNλ in the bronchoalveolar lavage during influenza/bacterial super-infection, suggesting that higher influenza viral burden drives a similar total IFNλ response regardless of IFNλ3 gene integrity. Interestingly, total IFNλ levels positively correlated with bacterial burden, while viral burden and bronchoalveolar lavage cellularity did not.ConclusionsThese data suggest IFNλ2 can compensate for IFNλ3 to mount an effective antiviral and defense, revealing a functional redundancy in these highly similar IFNλ subtypes. Further, the IFNλ response to influenza, as opposed to changes in cellular inflammation or viral load, significantly correlates with susceptibility to bacterial super-infection. Moreover, the IFNλ response is regulated and involves redundant subtypes, suggesting it is of high importance to pulmonary pathogen defense.

Immuno‐genetic importance of Th17 in susceptibility to TB

AbstractTuberculosis is a highly infectious disease caused by Mycobacterium tuberculosis (M. tb) which is infecting around one‐third of the world population. The majority of individuals develop latent tuberculosis infection (LTBI), but only 10% of LTBI individuals develop active TB. Household contacts (HHC) of TB patients are 10‐60 times more likely to develop the disease than non exposed individuals. Dendritic cells strengthen the immune response against M. tb through the stimulation of CD4+T cells, which differentiate into different types of T helper cells (Th) such as Th1, Th2 and Th17 lineages. Th17 cells play an important role in coordinating pulmonary immune defence and enhance the expression of cytokines (IL‐17A, IL‐17F, IL‐21 and IL‐22), chemokines and antimicrobial peptides that lead to phagocytosis of M. tb. Previous studies have reported that Th17 polymorphisms are associated with TB susceptibility. In this review, we focused on the immuno‐genetic importance of Th17 in TB and screening the HHCfor Th17 genetic variants may help for the early detection of TB infection in individuals who are at risk.

Ramping Up Antimicrobial Peptides Against Severe Acute Respiratory Syndrome Coronavirus-2.

Human-derived antimicrobial peptides (AMPs), such as defensins and cathelicidin LL-37, are members of the innate immune system and play a crucial role in early pulmonary defense against viruses. These AMPs achieve viral inhibition through a variety of mechanisms including, but not limited to, direct binding to virions, binding to and modulating host cell-surface receptors, blocking viral replication, and aggregation of viral particles and indirectly by functioning as chemokines to enhance or curb adaptive immune responses. Given the fact that we are in a pandemic of unprecedented severity and the urgent need for therapeutic options to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), naturally expressed AMPs and their derivatives have the potential to combat coronavirus disease 2019 (COVID-19) and impede viral infectivity in various ways. Provided the fact that development of effective treatments is an urgent public health priority, AMPs and their derivatives are being explored as potential prophylactic and therapeutic candidates. Additionally, cell-based platforms such as human mesenchymal stem cell (hMSC) therapy are showing success in saving the lives of severely ill patients infected with SARS-CoV-2. This could be partially due to AMPs released from hMSCs that also act as immunological rheostats to modulate the host inflammatory response. This review highlights the utilization of AMPs in strategies that could be implemented as novel therapeutics, either alone or in combination with other platforms, to treat CoV-2–infected individuals.

Vaping, SARS-CoV-2, and Multisystem Inflammatory Syndrome: A Perfect Storm.

The use of electronic cigarettes (e-cigarettes) and vaping among adolescents has risen exponentially in the last decade. E-cigarette flavors has driven adolescents to use these convenient, USB-like devices, designed to create a desired social image, while being seemingly unaware of the serious health consequences of their behavior. Vaping impacts protective pulmonary barriers by attenuating the mucociliary clearance and by increasing peribronchial inflammation and fibrosis. The recent SARS-CoV-2 (COVID-19) pandemic has been characterized by a plethora of unusual disease presentations. Among them, a unique presentation seen exclusively in children and adolescents was multisystem inflammatory syndrome (MIS-C). Seventy percent of adolescents who had MIS-C also had acute respiratory distress syndrome (ARDS), and we speculate that there may exist common denominator that links MIS-C and adolescents: the use of e-cigarettes. The virus targets the angiotensin converting receptor (ACE receptor), and studies have shown nicotine-based e-cigarettes or vaping cause oxidative stress and resulting in the upregulation of ACE2, which might worsen ARDS in MIS-C. Our mini-review highlights that adolescents using e-cigarette have alterations in their pulmonary defenses against SARS-CoV-2: an upregulation of the ACE2 receptors, the primary target of SARS-CoV-2. Their compromised immune system makes them more uniquely vulnerable to Covid-19 related MIS-C, increasing their risk for ARDS and related morbidities. Currently, studies have shown an association between MIS-C and vaping, we speculate that adolescents who vape/smoke might be especially vulnerable to serious respiratory symptoms if they develop a hyper-inflammatory state MIS-C.