scholarly journals Circadian regulation of lung repair and regeneration

2021 ◽  
Author(s):  
Amruta Naik ◽  
Kaitlyn Forrest ◽  
Yasmine Issah ◽  
Utham Valekunja ◽  
Akhilesh B Reddy ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Influenza A ◽  
Acute Inflammation ◽  
Viral Infections ◽  
Population Level ◽  
Lung Repair ◽  
Circadian Control ◽  
First Time ◽  
Critical Process

Optimal lung repair and regeneration is essential for recovery from viral infections such as that induced by influenza A virus (IAV). We have previously demonstrated that lung inflammation induced by IAV is under circadian control. However, it is not known if the circadian clock exerts its influence on lung repair and regenerative processes independent of acute inflammation from IAV. Here, we demonstrate for the first time that lung organoids have a functional clock as they mature and that the absence of an intact circadian clock impairs regenerative capacity. Using several models of circadian disruption, we show that with the absence of an intact clock lung proliferation is disrupted. Further, we find that the circadian clock acts through direct control of the Wnt/β-catenin pathway. We speculate, that adding the circadian dimension to the critical process of lung repair and regeneration will lead to novel therapies and improve outcomes. Finally, we use data from UK Biobank to demonstrate at the population level, the role of poor circadian rhythms in mediating negative outcomes following lung infection.

scholarly journals Circadian Clock Regulates Inflammation and the Development of Neurodegeneration

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiao-Lan Wang ◽  
Lianjian Li
Keyword(s):  
Circadian Clock ◽  
Immune Cells ◽  
Brain Function ◽  
Cellular Tissue ◽  
Physiological Processes ◽  
Circadian Control ◽  
Prevention And Treatment ◽  
Potential Strategy ◽  
Peripheral Immune Cells

The circadian clock regulates numerous key physiological processes and maintains cellular, tissue, and systemic homeostasis. Disruption of circadian clock machinery influences key activities involved in immune response and brain function. Moreover, Immune activation has been closely linked to neurodegeneration. Here, we review the molecular clock machinery and the diurnal variation of immune activity. We summarize the circadian control of immunity in both central and peripheral immune cells, as well as the circadian regulation of brain cells that are implicated in neurodegeneration. We explore the important role of systemic inflammation on neurodegeneration. The circadian clock modulates cellular metabolism, which could be a mechanism underlying circadian control. We also discuss the circadian interventions implicated in inflammation and neurodegeneration. Targeting circadian clocks could be a potential strategy for the prevention and treatment of inflammation and neurodegenerative diseases.

scholarly journals A functional spleen contributes to afucosylated IgG in humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iwona Wojcik ◽  
David E. Schmidt ◽  
Lisa A. de Neef ◽  
Minke A. E. Rab ◽  
Bob Meek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Immune Cell ◽  
Lymphoid Organ ◽  
Immune Effector ◽  
Adaptive Immune ◽  
Wide Range ◽  
Humoral Responses ◽  
First Time

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.

Activation of the aryl hydrocarbon receptor increases pulmonary neutrophilia and diminishes host resistance to influenza A virus

2005 ◽  
Vol 289 (1) ◽  
pp. L111-L124 ◽  
Author(s):  
Sabine Teske ◽  
Andrea A. Bohn ◽  
Jean F. Regal ◽  
Joshua J. Neumiller ◽  
B. Paige Lawrence
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Influenza A Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Neutrophil Function ◽  
Aryl Hydrocarbon ◽  
Potent Agonist

Unlike their role in bacterial infection, less is known about the role of neutrophils during pulmonary viral infection. Exposure to pollutant 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD, dioxin) results in excess neutrophils in the lungs of mice infected with influenza A virus. TCDD is the most potent agonist for the aryl hydrocarbon receptor (AhR), and exposure to AhR ligands has been correlated with exacerbated inflammatory lung diseases. However, knowledge of the effects of AhR agonists on neutrophils is limited. Likewise, the factors regulating neutrophil responses during respiratory viral infections are not well characterized. To address these knowledge gaps, we determined the in vivo levels of KC, MIP-1α, MIP-2, LIX, IL-6, and C5a in infected mouse lungs. Our data show that these neutrophil chemoattractants are generally produced transiently in the lung within 12–24 h of infection. We also report that expression of CD11a, CD11b, CD49d, CD31, and CD38 is increased on pulmonary neutrophils in response to influenza virus. Using AhR-deficient mice, we demonstrate that excess neutrophilia in the lung is mediated by activation of the AhR and that this enhanced neutrophilia correlates directly with decreased survival in TCDD-exposed mice. Although AhR activation results in more neutrophils in the lungs, we show that this is not mediated by deregulation in levels of common neutrophil chemoattractants, expression of adhesion molecules on pulmonary neutrophils, or delayed death of neutrophils. Likewise, exposure to TCDD did not enhance pulmonary neutrophil function. This study provides an important first step in elucidating the mechanisms by which AhR agonists exacerbate pulmonary inflammatory responses.

scholarly journals Successive Inoculations of Pigs with Porcine Reproductive and Respiratory Syndrome Virus 1 (PRRSV-1) and Swine H1N2 Influenza Virus Suggest a Mutual Interference between the Two Viral Infections

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2169
Author(s):  
Juliette Bougon ◽  
Céline Deblanc ◽  
Patricia Renson ◽  
Stéphane Quéguiner ◽  
Stéphane Gorin ◽  
...  
Keyword(s):  
Influenza A ◽  
Viral Infections ◽  
Clinical Signs ◽  
Swine Influenza ◽  
Time Correlation ◽  
Respiratory Syndrome Virus ◽  
Cell Mediated Immune Response ◽  
Specific Pathogen ◽  
Porcine Respiratory

Porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza A virus (swIAV) are major pathogens of the porcine respiratory disease complex, but little is known on their interaction in super-infected pigs. In this study, we investigated clinical, virological and immunological outcomes of successive infections with PRRSV-1 and H1N2 swIAV. Twenty-four specific pathogen-free piglets were distributed into four groups and inoculated either with PRRSV at study day (SD) 0, or with swIAV at SD8, or with PRRSV and swIAV one week apart at SD0 and SD8, respectively, or mock-inoculated. In PRRSV/swIAV group, the clinical signs usually observed after swIAV infection were attenuated while higher levels of anti-swIAV antibodies were measured in lungs. Concurrently, PRRSV multiplication in lungs was significantly affected by swIAV infection, whereas the cell-mediated immune response specific to PRRSV was detected earlier in blood, as compared to PRRSV group. Moreover, levels of interferon (IFN)-α measured from SD9 in the blood of super-infected pigs were lower than those measured in the swIAV group, but higher than in the PRRSV group at the same time. Correlation analyses suggested an important role of IFN-α in the two-way interference highlighted between both viral infections.

scholarly journals Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Eric D. Abston ◽  
Michael J. Coronado ◽  
Adriana Bucek ◽  
Djahida Bedja ◽  
Jaewook Shin ◽  
...  
Keyword(s):  
Viral Infections ◽  
Heart Function ◽  
Viral Myocarditis ◽  
Alternative Activation ◽  
Toll Like Receptor ◽  
T Helper ◽  
Chronic Myocarditis ◽  
First Time ◽  
Deficient Mice

Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR)3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3) myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL)-4-dominant T helper (Th)2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

scholarly journals Susceptibility for Some Infectious Diseases in Patients With Diabetes: The Key Role of Glycemia

2021 ◽  
Vol 9 ◽  
Author(s):  
Jesús Chávez-Reyes ◽  
Carlos E. Escárcega-González ◽  
Erika Chavira-Suárez ◽  
Angel León-Buitimea ◽  
Priscila Vázquez-León ◽  
...  
Keyword(s):  
Immune System ◽  
Infectious Diseases ◽  
Influenza A ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Clinical Findings ◽  
Uncontrolled Diabetes ◽  
Patients With Diabetes ◽  
The Impact

Uncontrolled diabetes results in several metabolic alterations including hyperglycemia. Indeed, several preclinical and clinical studies have suggested that this condition may induce susceptibility and the development of more aggressive infectious diseases, especially those caused by some bacteria (including Chlamydophila pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae, among others) and viruses [such as coronavirus 2 (CoV2), Influenza A virus, Hepatitis B, etc.]. Although the precise mechanisms that link glycemia to the exacerbated infections remain elusive, hyperglycemia is known to induce a wide array of changes in the immune system activity, including alterations in: (i) the microenvironment of immune cells (e.g., pH, blood viscosity and other biochemical parameters); (ii) the supply of energy to infectious bacteria; (iii) the inflammatory response; and (iv) oxidative stress as a result of bacterial proliferative metabolism. Consistent with this evidence, some bacterial infections are typical (and/or have a worse prognosis) in patients with hypercaloric diets and a stressful lifestyle (conditions that promote hyperglycemic episodes). On this basis, the present review is particularly focused on: (i) the role of diabetes in the development of some bacterial and viral infections by analyzing preclinical and clinical findings; (ii) discussing the possible mechanisms by which hyperglycemia may increase the susceptibility for developing infections; and (iii) further understanding the impact of hyperglycemia on the immune system.

scholarly journals Role of Viral Protein-Protein Interactions and Possible Targets for New Therapeutics

2021 ◽  
Vol 2 (2) ◽  
pp. 1-15
Author(s):  
Rehan Zafar Paracha ◽  
Fahed Parvaiz ◽  
Babar Aslam ◽  
Ayesha Obaid ◽  
Sidra Qureshi ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Viral Protein ◽  
Influenza A ◽  
Viral Infections ◽  
Treatment Options ◽  
Interaction Network ◽  
Viral Proteins ◽  
Protein Protein Interactions ◽  
Virus Influenza

Viral infections are the cause of serious infirmities in humans and kill millions of people every year. Management of viral diseases is one of the challenges faced by the whole world which needs improvement in prevention and treatment options. Complete understanding of the consequences of viral proteins interaction network on host physiology is essential. Towards this goal, deciphering viral protein-protein interactions is one of the perspective which can help in our understanding about the basis of viral pathogenesis and the development of new antivirals. Indeed, viral infection network based on viral-viral proteins will provide an elusive and investigative framework to articulate rationalize drug discovery based on proteomics scale of viruses. In this study, proteomics a collection of viral-viral protein interactions reporting different studies of Hepatitis C virus, Influenza A virus, Dengue virus and SARS Coronavirus. Our effort of protein-interactions was focused on different studies reporting interactions between viral proteins encoded by the viruses under study. The study is integrated with a broad and original literature-curated data of viral-viral protein (197 non-redundant) interactions.

scholarly journals Tetraspanins: Host Factors in Viral Infections

2021 ◽  
Vol 22 (21) ◽  
pp. 11609
Author(s):  
ChihSheng New ◽  
Zhao-Yong Lee ◽  
Kai Sen Tan ◽  
Amanda Huee-Ping Wong ◽  
De Yun Wang ◽  
...  
Keyword(s):  
Influenza A ◽  
Viral Infections ◽  
Syncytium Formation ◽  
Life Cycles ◽  
Host Factors ◽  
Relative Contribution ◽  
Immunodeficiency Virus ◽  
Membrane Attachment ◽  
Compare And Contrast

Tetraspanins are transmembrane glycoproteins that have been shown increasing interest as host factors in infectious diseases. In particular, they were implicated in the pathogenesis of both non-enveloped (human papillomavirus (HPV)) and enveloped (human immunodeficiency virus (HIV), Zika, influenza A virus, (IAV), and coronavirus) viruses through multiple stages of infection, from the initial cell membrane attachment to the syncytium formation and viral particle release. However, the mechanisms by which different tetraspanins mediate their effects vary. This review aimed to compare and contrast the role of tetraspanins in the life cycles of HPV, HIV, Zika, IAV, and coronavirus viruses, which cause the most significant health and economic burdens to society. In doing so, a better understanding of the relative contribution of tetraspanins in virus infection will allow for a more targeted approach in the treatment of these diseases.

scholarly journals The Role of Bcl-xL Protein in Viral Infections

2021 ◽  
Vol 22 (4) ◽  
pp. 1956
Author(s):  
Zbigniew Wyżewski ◽  
Weronika Świtlik ◽  
Matylda Barbara Mielcarska ◽  
Karolina Paulina Gregorczyk-Zboroch
Keyword(s):  
Influenza A ◽  
Viral Infections ◽  
Treatment Strategies ◽  
Systemic Infection ◽  
Apoptosis Pathway ◽  
Barr Virus ◽  
Intrinsic Apoptosis Pathway ◽  
Epstein Barr ◽  
The Impact

Bcl-xL represents a family of proteins responsible for the regulation of the intrinsic apoptosis pathway. Due to its anti-apoptotic activity, Bcl-xL co-determines the viability of various virally infected cells. Their survival may determine the effectiveness of viral replication and spread, dynamics of systemic infection, and viral pathogenesis. In this paper, we have reviewed the role of Bcl-xL in the context of host infection by eight different RNA and DNA viruses: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), influenza A virus (IAV), Epstein-Barr virus (EBV), human T-lymphotropic virus type-1 (HTLV-1), Maraba virus (MRBV), Schmallenberg virus (SBV) and coronavirus (CoV). We have described an influence of viral infection on the intracellular level of Bcl-xL and discussed the impact of Bcl-xL-dependent cell survival control on infection-accompanying pathogenic events such as tissue damage or oncogenesis. We have also presented anti-viral treatment strategies based on the pharmacological regulation of Bcl-xL expression or activity.

scholarly journals Clocks, Viruses, and Immunity: Lessons for the COVID-19 Pandemic

2021 ◽  
pp. 074873042098766
Author(s):  
Shaon Sengupta ◽  
Louise Ince ◽  
Francesca Sartor ◽  
Helene Borrmann ◽  
Xiaodong Zhuang ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Viral Infections ◽  
Current Knowledge ◽  
Large Body ◽  
Research Priorities ◽  
Biological Rhythms ◽  
Host Susceptibility ◽  
Host Responses ◽  
Anticipatory Systems

Circadian rhythms are evolutionarily conserved anticipatory systems that allow the host to prepare and respond to threats in its environment. This article summarizes a European Biological Rhythms Society (EBRS) workshop held in July 2020 to review current knowledge of the interplay between the circadian clock and viral infections to inform therapeutic strategies against SARS-CoV-2 and COVID-19. A large body of work supports the role of the circadian clock in regulating various aspects of viral replication, host responses, and associated pathogenesis. We review the evidence describing the multifaceted role of the circadian clock, spanning host susceptibility, antiviral mechanisms, and host resilience. Finally, we define the most pressing research questions and how our knowledge of chronobiology can inform key translational research priorities.

Sign in / Sign up

Export Citation Format

Share Document