Innate And Adaptive Immunity
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2022 ◽  
Ulrik Fahnoe ◽  
Andreas Ronit ◽  
Ronan M.G. Berg ◽  
Sofie E.G. Joergensen ◽  
Trine H. Mogensen ◽  

Background: It is unknown whether the complex immunopathogenesis of COVID-19 acute respiratory distress syndrome (CARDS) differs from that of non-COVID-19 ARDS. Moreover, the effects of systemic dexamethasone (DXM) treatment on pulmonary immunity in COVID-19 remain insufficiently understood. Objective: To understand immune regulation in the lungs of CARDS and critically ill non-COVID-19 patients through gene expression profiling. Methods: Transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid (BALF) from 21 patients: 13 with CARDS (non-DXM or DXM-treated) and 8 with non-COVID-19 ARDS and/or sepsis (all non-DXM-treated). Functional analysis was performed using gene ontology and a blood transcription module, and gene expression of select pro-inflammatory cytokines, interferon-stimulated genes (ISGs) and auto-IFN antibodies were assessed. Results: Median (range) time of COVID-19 symptoms were 11 (8-20) days and BALF was collected 32 (6-65) hours after intubation. We found 550 and 2173 differentially expressed genes in patients with non-DXM-CARDS and DXM-CARDS, respectively. DXM-CARDS was characterized by upregulation of genes related to pulmonary innate and adaptive immunity, notably B-cell and complement pathway activation, antigen presentation, phagocytosis and FC-gamma receptor signalling. Pro-inflammatory genes were not differentially expressed in CARDS vs. non-COVID-19, nor did they differ according to DXM. Most ISGs were specifically upregulated in CARDS, particularly in non-DXM-CARDS. Auto-IFN autoantibodies were detectable in BALF of some CARDS patients. Conclusion: DXM treatment was not associated with regulation of pro-inflammatory pathways in CARDS but with regulation of other specific local innate and adaptive immune responses. These results challenge the concept of a COVID-19 specific cytokine storm.

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 274
Quang Vo Nguyen ◽  
Li Chuin Chong ◽  
Yan-Yan Hor ◽  
Lee-Ching Lew ◽  
Irfan A. Rather ◽  

Coronavirus disease 2019 (COVID-19) was declared a pandemic at the beginning of 2020, causing millions of deaths worldwide. Millions of vaccine doses have been administered worldwide; however, outbreaks continue. Probiotics are known to restore a stable gut microbiota by regulating innate and adaptive immunity within the gut, demonstrating the possibility that they may be used to combat COVID-19 because of several pieces of evidence suggesting that COVID-19 has an adverse impact on gut microbiota dysbiosis. Thus, probiotics and their metabolites with known antiviral properties may be used as an adjunctive treatment to combat COVID-19. Several clinical trials have revealed the efficacy of probiotics and their metabolites in treating patients with SARS-CoV-2. However, its molecular mechanism has not been unraveled. The availability of abundant data resources and computational methods has significantly changed research finding molecular insights between probiotics and COVID-19. This review highlights computational approaches involving microbiome-based approaches and ensemble-driven docking approaches, as well as a case study proving the effects of probiotic metabolites on SARS-CoV-2.

2022 ◽  
Tamara Zorbaz ◽  
Nimrod Madrer ◽  
Hermona Soreq

Inflammatory stimuli and consequent pro-inflammatory immune responses may facilitate neurodegeneration and threaten survival following pathogen infection or trauma, but potential controllers preventing these risks are incompletely understood. Here, we argue that small RNA regulators of acetylcholine (ACh) signaling, including microRNAs and transfer RNA fragments may tilt the balance between innate and adaptive immunity, avoid chronic inflammation and prevent the neuroinflammation-mediated exacerbation of many neurological diseases. While the restrictive permeability of the blood-brain barrier protects the brain from peripheral immune events, this barrier can be disrupted by inflammation and is weakened with age. The consequently dysregulated balance between pro- and anti-inflammatory processes may modify the immune activities of brain microglia, astrocytes, perivascular macrophages, oligodendrocytes and dendritic cells, leading to neuronal damage. Notably, the vagus nerve mediates the peripheral cholinergic anti-inflammatory reflex and underlines the consistent control of body-brain inflammation by pro-inflammatory cytokines, which affect cholinergic functions; therefore, the disruption of this reflex can exacerbate cognitive impairments such as attention deficits and delirium. RNA regulators can contribute to re-balancing the cholinergic network and avoiding its chronic deterioration, and their activities may differ between men and women and/or wear off with age. This can lead to hypersensitivity of aged patients to inflammation and higher risks of neuroinflammatory-driven cholinergic impairments such as delirium and dementia following COVID-19 infection. The age- and sex-driven differences in post-transcriptional RNA regulators of cholinergic elements may hence indicate new personalized therapeutic options for neuroinflammatory diseases.

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 100
Anna Alwani ◽  
Aneta Andreasik ◽  
Rafał Szatanek ◽  
Maciej Siedlar ◽  
Monika Baj-Krzyworzeka

Monocytes represent a heterogeneous population of blood cells that provide a link between innate and adaptive immunity. The unique potential of monocytes as both precursors (e.g., of macrophages) and effector cells (as phagocytes or cytotoxic cells) makes them an interesting research and therapeutic target. At the site of a tumor, monocytes/macrophages constitute a major population of infiltrating leukocytes and, depending on the type of tumor, may play a dual role as either a bad or good indicator for cancer recovery. The functional activity of monocytes and macrophages derived from them is tightly regulated at the transcriptional and post-transcriptional level. This review summarizes the current understanding of the role of small regulatory miRNA in monocyte formation, maturation and function in health and cancer development. Additionally, signatures of miRNA-based monocyte subsets and the influence of exogenous miRNA generated in the tumor environment on the function of monocytes are discussed.

2022 ◽  
Wei-Jia Luo ◽  
Sung-Liang Yu ◽  
Chia-Ching Chang ◽  
Min-Hui Chien ◽  
Keng-Mao Liao ◽  

Heat shock protein (HSP) 40 has emerged as a key actor in both innate and adaptive immunity, whereas the role of HLJ1, a molecular chaperone in HSP40 family, in modulating endotoxin–induced sepsis severity is still unclear. Here, we use single-cell RNA sequencing to characterize mouse liver nonparenchymal cell populations under LPS (lipopolysaccharide) stimulation, and show that HLJ1 deletion affected IFN-γ-related gene signatures in distinct immune cell clusters. HLJ1 deficiency also leads to reduced serum levels of IL-12 in LPS-treated mice, contributing to dampened production of IFN-γ in natural killer cells but not CD4+ or CD8+ T cells, and subsequently to improved survival rate. Adoptive transfer of HLJ1-deleted macrophages into LPS-treated mice results in reduced IL-12 and IFN-γ levels and protects the mice from IFN-γ–dependent mortality. In the context of molecular mechanisms, HLJ1 is an LPS-inducible protein in macrophages and converts misfolded IL-12p35 homodimers to monomers, which maintains bioactive IL-12p70 heterodimerization and secretion. This study suggests HLJ1 causes IFN-γ–dependent septic lethality by promoting IL-12 heterodimerization, and targeting HLJ1 has therapeutic potential in inflammatory diseases involving activating IL-12/IFN-γ axis.

eLife ◽  
2021 ◽  
Vol 10 ◽  
Chansavath Phetsouphanh ◽  
Prabhjeet Phalora ◽  
Carl-Philipp Hackstein ◽  
John Thornhill ◽  
Mee Ling Munier ◽  

Human MAIT cells sit at the interface between innate and adaptive immunity, are polyfunctional and are capable of killing pathogen infected cells via recognition of the Class IB molecule MR1. MAIT cells have recently been shown to possess an antiviral protective role in vivo and we therefore sought to explore this in relation to HIV-1 infection. There was marked activation of MAIT cells in vivo in HIV-1 infected individuals, which decreased following ART. Stimulation of THP1 monocytes with R5 tropic HIVBAL potently activated MAIT cells in vitro. This activation was dependent on IL-12 and IL-18 but was independent of the TCR. Upon activation, MAIT cells were able to up-regulate granzyme B, IFNg and HIV-1 restriction factors CCL3, 4 and 5. Restriction factors produced by MAIT cells inhibited HIV-1 infection of primary PBMCs and immortalized target cells in vitro. These data reveal MAIT cells to be an additional T cell population responding to HIV-1, with a potentially important role in controlling viral replication at mucosal sites.

2021 ◽  
Vol 12 ◽  
Andreina Bruno ◽  
Giuliana Ferrante ◽  
Serena Di Vincenzo ◽  
Elisabetta Pace ◽  
Stefania La Grutta

Leptin is a pleiotropic adipocytokine involved in several physiologic functions, with a known role in innate and adaptive immunity as well as in tissue homeostasis. Long- and short-isoforms of leptin receptors are widely expressed in many peripheral tissues and organs, such as the respiratory tract. Similar to leptin, microbiota affects the immune system and may interfere with lung health through the bidirectional crosstalk called the “gut-lung axis.” Obesity leads to impaired protective immunity and altered susceptibility to pulmonary infections, as those by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although it is known that leptin and microbiota link metabolism and lung health, their role within the SARS-CoV2 coronavirus disease 2019 (COVID-19) deserves further investigations. This review aimed to summarize the available evidence about: (i) the role of leptin in immune modulation; (ii) the role of gut microbiota within the gut-lung axis in modulating leptin sensitivity; and (iii) the role of leptin in the pathophysiology of COVID-19.

2021 ◽  
Vol 0 (0) ◽  
Zuzanna Rząd ◽  
Joanna Rog

Abstract Introduction: Anorexia nervosa (AN) is a mental disorder with the highest death rate. The characteristic feature of AN is endocrine dysregulations, including changes in adipose-tissue secreted hormones, especially adipokines. The most widely studied of them is leptin whose role in the pathophysiology and prognosis of AN is confirmed in more and more studies. The aim of the study was to summarize the role of endocrine disruptions with particular emphasis on leptin in the pathophysiology of AN. Material and methods: For the literature review, the electronic databases PubMed, Cochrane and Google Scholar search were used with the following keywords: eating disorders, adipokines, leptin, metreleptin, satiety, hunger, anorexia, obesity, for studies listed from database inception to October 2021. Results: Leptin, produced mainly by white adipose tissue, inhibits the hunger center in the hypothalamus by negative feedback with ghrelin secreted by the gastrointestinal tract. Leptin is involved in numerous biological functions, including body weight regulation, innate and adaptive immunity regulation, reproduction, and bone formation. Studies confirm decreased leptin levels in AN individuals. In recent years, extensive experience has been gained with leptin as a drug in clinical trials. The studies suggested that treatment can restore menstrual function and bone health and improve mood with unclear body weight effects. Conclusions: Focusing on leptin-related changes is a promising approach to improve AN management. Assessment of leptin levels in AN patients could be a useful tool for therapy monitoring. Treatment with leptin could reverse unfavourable changes induced by diet restriction, including mood symptoms, loss of bone mass and menstrual function. However, the results of these studies need confirmation on larger groups of patients.

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