Type II alveolar cell MHCII improves respiratory viral disease outcomes while exhibiting limited antigen presentation

AbstractType II alveolar cells (AT2s) are critical for basic respiratory homeostasis and tissue repair after lung injury. Prior studies indicate that AT2s also express major histocompatibility complex class II (MHCII) molecules, but how MHCII expression by AT2s is regulated and how it contributes to host defense remain unclear. Here we show that AT2s express high levels of MHCII independent of conventional inflammatory stimuli, and that selective loss of MHCII from AT2s in mice results in modest worsening of respiratory virus disease following influenza and Sendai virus infections. We also find that AT2s exhibit MHCII presentation capacity that is substantially limited compared to professional antigen presenting cells. The combination of constitutive MHCII expression and restrained antigen presentation may position AT2s to contribute to lung adaptive immune responses in a measured fashion, without over-amplifying damaging inflammation.

Download Full-text

Type II alveolar cells with constitutive expression of MHCII and limited antigen presentation capacity contribute to improved respiratory viral disease outcomes

10.1101/2021.03.18.435984 ◽

2021 ◽

Author(s):

Sushila A Toulmin ◽

Chaitali Bhadiadra ◽

Andrew J Paris ◽

Jeffrey H Lin ◽

Jeremy Katzen ◽

...

Keyword(s):

Sendai Virus ◽

Virus Disease ◽

Constitutive Expression ◽

Viral Disease ◽

Type Ii ◽

Virus Infections ◽

Alveolar Cells ◽

Type Ii Alveolar Cells ◽

Respiratory Homeostasis ◽

Mhcii Expression

Type II alveolar cells (AT2s) are critical for basic respiratory homeostasis and tissue repair after lung injury. Prior studies indicate that AT2s also express major histocompatibility complex II (MHCII) molecules, but how MHCII expression by AT2s is regulated and how it contributes to host defense remain unclear. Here we show that AT2s express high levels of MHCII independent of conventional inflammatory stimuli, and that selective loss of MHCII from AT2s in mice results in the worsening of respiratory virus disease following influenza and Sendai virus infections. We also find that AT2s exhibit MHCII presentation capacity that is substantially limited in comparison to professional antigen presenting cells. The combination of constitutive MHCII expression and restrained presentation may position AT2s to contribute to lung adaptive immune responses in a measured fashion, without over-amplifying damaging inflammation.

Download Full-text

Alveolar Epithelial Cell Type II as main target of SARS-CoV-2 virus and COVID-19 development via NF-Kb pathway deregulation.

10.21203/rs.3.rs-77539/v1 ◽

2020 ◽

Author(s):

Maurizio Carcaterra ◽

Cristina Caruso

Keyword(s):

Molecular Mechanisms ◽

Virus Disease ◽

Clinical Manifestations ◽

Alveolar Epithelial Cells ◽

Type Ii ◽

Cell Type ◽

Alveolar Cells ◽

Alveolar Epithelial ◽

Corona Virus ◽

Number Of Patients

Abstract Background: The Corona Virus Disease (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) requires a rapid solutionand global collaborative efforts in order to define preventive and treatment strategies.Methods: One of the major challenges of this disease is the high number of patients needing advanced respiratory support due to the Acute Respiratory Distress Syndrome (ARDS) as the lung is the major –although not exclusive-target of the virus. The molecular mechanisms, pathogenic drivers and the target cell type(s) in SARSCoV-2 infection are still poorly understood, but the development of a “hyperactive” immune response is proposed to play a role in the evolution of the disease and it is envisioned as a major cause of morbidity and mortality.Results: Here we propose a theory by which the main targets for SARS-CoV-2 are the Type II Alveolar Epithelial Cells and the clinical manifestations of the syndrome are a direct consequence of their involvement. We hypotize the existence of a vicious cycle by which once alveolar damage starts in AEC II cells, the inflammatory state is supported by macrophage proinflammatory polarization (M1), cytokines release and by the activation of the NF-κB pathway.Conclusions: If this theory is confirmed, future therapeutic efforts can be directed to target Type 2 alveolar cells and the molecular pathogenic drivers associated with their dysfunction with currently available therapeutic strategies.

Download Full-text

Faculty Opinions recommendation of Differential antigen presentation regulates the changing patterns of CD8+ T cell immunodominance in primary and secondary influenza virus infections.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1014749.195402 ◽

2003 ◽

Author(s):

Andrea Sant

Keyword(s):

Influenza Virus ◽

T Cell ◽

Antigen Presentation ◽

Cd8 T Cell ◽

Virus Infections ◽

Changing Patterns

Download Full-text

Faculty Opinions recommendation of Differential antigen presentation regulates the changing patterns of CD8+ T cell immunodominance in primary and secondary influenza virus infections.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1014749.194534 ◽

2003 ◽

Author(s):

Peter Van Endert

Keyword(s):

Influenza Virus ◽

T Cell ◽

Antigen Presentation ◽

Cd8 T Cell ◽

Virus Infections ◽

Changing Patterns

Download Full-text

Protection of mice from respiratory Sendai virus infections by recombinant vaccinia viruses.

Journal of Virology ◽

10.1128/jvi.71.1.832-838.1997 ◽

1997 ◽

Vol 71 (1) ◽

pp. 832-838 ◽

Cited By ~ 11

Author(s):

S I Takao ◽

K Kiyotani ◽

T Sakaguchi ◽

Y Fujii ◽

M Seno ◽

...

Keyword(s):

Sendai Virus ◽

Virus Infections ◽

Recombinant Vaccinia ◽

Vaccinia Viruses

Download Full-text

Innate Immunity in Children and the Role of ACE2 Expression in SARS-CoV-2 Infection

Pediatric Reports ◽

10.3390/pediatric13030045 ◽

2021 ◽

Vol 13 (3) ◽

pp. 363-382

Author(s):

Mario Dioguardi ◽

Angela Pia Cazzolla ◽

Claudia Arena ◽

Diego Sovereto ◽

Giorgia Apollonia Caloro ◽

...

Keyword(s):

Innate Immunity ◽

Viral Infections ◽

Respiratory Infections ◽

Viral Disease ◽

Receptor Expression ◽

Virus Infections ◽

Search Terms ◽

Bibliographic Search ◽

Meta Analyses

COVID-19 (Coronavirus Disease 2019) is an emerging viral disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to severe respiratory infections in humans. The first reports came in December 2019 from the city of Wuhan in the province of Hubei in China. It was immediately clear that children developed a milder disease than adults. The reasons for the milder course of the disease were attributed to several factors: innate immunity, difference in ACE2 (angiotensin-converting enzyme II) receptor expression, and previous infections with other common coronaviruses (CovH). This literature review aims to summarize aspects of innate immunity by focusing on the role of ACE2 expression and viral infections in children in modulating the antibody response to SARS-CoV-2 infection. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles deemed potentially eligible were considered, including those dealing with COVID-19 in children and providing more up-to-date and significant data in terms of epidemiology, prognosis, course, and symptoms, focusing on the etiopathogenesis of SARS-CoV-2 disease in children. The bibliographic search was conducted using the search engines PubMed and Scopus. The following search terms were entered in PubMed and Scopus: COVID-19 AND ACE2 AND Children; COVID-19 AND Immunity innate AND children. The search identified 857 records, and 18 studies were applicable based on inclusion and exclusion criteria that addressed the issues of COVID-19 concerning the role of ACE2 expression in children. The scientific literature agrees that children develop milder COVID-19 disease than adults. Milder symptomatology could be attributed to innate immunity or previous CovH virus infections, while it is not yet fully understood how the differential expression of ACE2 in children could contribute to milder disease.

Download Full-text

Fractal Dimensions of Subviral Particle Movement

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2018-0020 ◽

2018 ◽

Vol 4 (1) ◽

pp. 79-82 ◽

Cited By ~ 1

Author(s):

Andreas Rausch ◽

Thomas Schanze

Keyword(s):

Virus Disease ◽

Fractal Dimensions ◽

Real Data ◽

Marburg Virus ◽

Virus Infections ◽

Fluorescence Image ◽

Good Potential ◽

Infected Cells ◽

Subviral Particle ◽

Subviral Particles

AbstractThe development of new medicines against virus infections like the Marburg virus disease requires an accurate knowledge of the respective pathogens. Conventionally, this process is very time expensive. In cooperation with the Virology of the Philipps-University in Marburg an automatic tracking algorithm for subviral particles in fluorescence image sequences was developed and programmed. To expand the benefit for the pharmaceutical researchers, also the trackevaluations need to be widely automated. In this work, a new parameterizing-method facing the fractal dimensions of spline interpolated subviral particle tracks is presented and tested with simulated and real data. The results reveal a good potential to classify tracks and, thus, types of subviral particles in infected cells.

Download Full-text

Respiratory Failure Due to Differentiation Arrest and Expansion of Alveolar Cells following Lung-Specific Loss of the Transcription Factor C/EBPα in Mice

Molecular and Cellular Biology ◽

10.1128/mcb.26.3.1109-1123.2006 ◽

2006 ◽

Vol 26 (3) ◽

pp. 1109-1123 ◽

Cited By ~ 45

Author(s):

Daniela S. Bassères ◽

Elena Levantini ◽

Hongbin Ji ◽

Stefano Monti ◽

Shannon Elf ◽

...

Keyword(s):

Transcription Factor ◽

Cell Differentiation ◽

Respiratory Failure ◽

Leucine Zipper ◽

Type I ◽

Type Ii ◽

Alveolar Cells ◽

Proliferating Cells ◽

Therapeutic Benefits ◽

Factor C

ABSTRACT The leucine zipper family transcription factor CCAAT enhancer binding protein alpha (C/EBPα) inhibits proliferation and promotes differentiation in various cell types. In this study, we show, using a lung-specific conditional mouse model of C/EBPα deletion, that loss of C/EBPα in the respiratory epithelium leads to respiratory failure at birth due to an arrest in the type II alveolar cell differentiation program. This differentiation arrest results in the lack of type I alveolar cells and differentiated surfactant-secreting type II alveolar cells. In addition to showing a block in type II cell differentiation, the neonatal lungs display increased numbers of proliferating cells and decreased numbers of apoptotic cells, leading to epithelial expansion and loss of airspace. Consistent with the phenotype observed, genes associated with alveolar maturation, survival, and proliferation were differentially expressed. Taken together, these results identify C/EBPα as a master regulator of airway epithelial maturation and suggest that the loss of C/EBPα could also be an important event in the multistep process of lung tumorigenesis. Furthermore, this study indicates that exploring the C/EBPα pathway might have therapeutic benefits for patients with respiratory distress syndromes.

Download Full-text

UPDATE ON CARDIOVASCULAR IMPLICATIONS OF COVID 19

10.36106/gjra/8013840 ◽

2021 ◽

pp. 238-242

Author(s):

Pradeep Kumar Radhakrishnan ◽

Gayathri Ananyajyothi Ambat ◽

Roshini Ambat ◽

Syed Ilas Basha ◽

Hema Prakash ◽

...

Keyword(s):

Virus Disease ◽

Systemic Vasculitis ◽

Myocardial Damage ◽

Viral Disease ◽

Cardiac Damage ◽

Corona Virus ◽

Global Pandemic ◽

Acute Myocardial Injury ◽

Exercise Induced

On March 11 2020 WHO declares corona viral disease as a global pandemic .COVID 19 pandemic has taken the world by storm and many countries like India is now experiencing a second surge due to mutant strains. Global health emergency has been precipitated by this corona virus disease caused by SARS CoV2.Acute and intermediate effects on cardiovascular system are becoming obvious with progression of time. SARS-CoV-2-related endothelial dysfunction results in an augmented risk for venous thromboembolism, systemic vasculitis, endothelial cell apoptosis, and inammation in various organs. Acute infections have troponin elevation more due to indirect cardiac damage though denite patterns of direct damage do exist. Intermediate evaluation in patients with resolved infections shows increased incidence of exercise induced arrhythmias and residual cardiovascular symptoms. The virus with its zoonotic origin based upon its genomic identity to bat derived SARS corona virus has a human to human transmission mode.ACE 2 receptors facilitate cellular entry and has been implicated in direct and indirect myocardial damage. Myocarditis, acute myocardial injury, arrhythmias and thromboembolism dominates the clinical picture. Role of imaging must be dened in relation to relevant clinical ndings. With arrival of vaccine and widespread vaccination global programs, we can look forward to understanding and managing long term complications of this disease. Prognostic implications of a resolved disease need to be evaluated by future studies.

Download Full-text