Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip

Bai, Haiqing; Si, Longlong; Jiang, Amanda; Belgur, Chaitra; Zhai, Yunhao; Plebani, Roberto; Oh, Crystal Yuri; Rodas, Melissa; Patil, Aditya; Nurani, Atiq; Gilpin, Sarah E.; Powers, Rani K.; Goyal, Girija; Prantil‐Baun, Rachelle; Ingber, Donald E.

doi:10.1038/s41467-022-29562-4

Cited by 57 publications

(59 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This platform was found to be useful in preclinical drug testing and screening. Recently, Bai et al were able to demonstrate physiological correlation between the mechanical breathing motions of lung tissues with host innate immunity using a human lung alveolus chip that experiences cyclic breathing-like deformations [ 20 ]. This marked a major advancement in the field when compared with static OOAC platforms as it revealed that breathing motions could suppress viral replication by activating protective innate immune responses in epithelial and endothelial cells [ 20 ].…”

Section: Types Of Ooac Devicesmentioning

confidence: 99%

Breakthroughs and Applications of Organ-on-a-Chip Technology

Koyilot¹,

Natarajan²,

Hunt

et al. 2022

Cells

View full text Add to dashboard Cite

Organ-on-a-chip (OOAC) is an emerging technology based on microfluid platforms and in vitro cell culture that has a promising future in the healthcare industry. The numerous advantages of OOAC over conventional systems make it highly popular. The chip is an innovative combination of novel technologies, including lab-on-a-chip, microfluidics, biomaterials, and tissue engineering. This paper begins by analyzing the need for the development of OOAC followed by a brief introduction to the technology. Later sections discuss and review the various types of OOACs and the fabrication materials used. The implementation of artificial intelligence in the system makes it more advanced, thereby helping to provide a more accurate diagnosis as well as convenient data management. We introduce selected OOAC projects, including applications to organ/disease modelling, pharmacology, personalized medicine, and dentistry. Finally, we point out certain challenges that need to be surmounted in order to further develop and upgrade the current systems.

show abstract

Section: Types Of Ooac Devicesmentioning

confidence: 99%

Breakthroughs and Applications of Organ-on-a-Chip Technology

Koyilot¹,

Natarajan²,

Hunt

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Fluid shear stress and other mechanical forces, such as lung rhythmic breathing motions, can be introduced. Moreover, immune cells can be perfused through the vascular channel [ 29 , 56 ] ( Figure 1 C). This model has been optimized and utilized for studies on respiratory diseases, including CF, COPD, and lung infections [ 14 , 29 , 57 , 58 ].…”

Section: Lung 3d Culturesmentioning

confidence: 99%

“…Moreover, immune cells can be perfused through the vascular channel [ 29 , 56 ] ( Figure 1 C). This model has been optimized and utilized for studies on respiratory diseases, including CF, COPD, and lung infections [ 14 , 29 , 57 , 58 ]. Additional respiratory organ-on-chips with slightly different structures have been built by other groups.…”

Section: Lung 3d Culturesmentioning

confidence: 99%

“…In addition to the 3D culture of lung cells under ALI, it includes vascular structures, allowing perfusion of drugs and immune cells under controlled shear, and it can be subjected to mechanical strain to mimic the respiratory cycle. This technology has been successfully applied to studies on COVID-19 [ 14 , 29 ], leading to significant advances in our knowledge of viral pneumonia and its treatment.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

3D Lung Tissue Models for Studies on SARS-CoV-2 Pathophysiology and Therapeutics

Plebani

Bai²,

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has provoked more than six million deaths worldwide and continues to pose a major threat to global health. Enormous efforts have been made by researchers around the world to elucidate COVID-19 pathophysiology, design efficacious therapy and develop new vaccines to control the pandemic. To this end, experimental models are essential. While animal models and conventional cell cultures have been widely utilized during these research endeavors, they often do not adequately reflect the human responses to SARS-CoV-2 infection. Therefore, models that emulate with high fidelity the SARS-CoV-2 infection in human organs are needed for discovering new antiviral drugs and vaccines against COVID-19. Three-dimensional (3D) cell cultures, such as lung organoids and bioengineered organs-on-chips, are emerging as crucial tools for research on respiratory diseases. The lung airway, small airway and alveolus organ chips have been successfully used for studies on lung response to infection by various pathogens, including corona and influenza A viruses. In this review, we provide an overview of these new tools and their use in studies on COVID-19 pathogenesis and drug testing. We also discuss the limitations of the existing models and indicate some improvements for their use in research against COVID-19 as well as future emerging epidemics.

show abstract

“…Influenza infection activates a number of host pathways, including the innate and adaptive immune responses, the induction of cytokines, and the activation of apoptosis [ 4 ]. The detection of viral particles (in particular nuclear acids) by toll-like receptors (TLR7) of the MyD88, NF-kB pathway [ 5 ], as well as cytosolic proteins such as RIG-I (DDX58) of the MDAF/MAVS pathway and their trigger of interferon expression via the activation of transcription factors including IRF3 and IRF7 [ 6 , 7 ], have been well studied.…”

Section: Introductionmentioning

confidence: 99%

Identification of Critical Genes and Pathways for Influenza A Virus Infections via Bioinformatics Analysis

Chen

Hao

et al. 2022

Viruses

View full text Add to dashboard Cite

Influenza A virus (IAV) requires the host cellular machinery for many aspects of its life cycle. Knowledge of these host cell requirements not only reveals molecular pathways exploited by the virus or triggered by the immune system but also provides further targets for antiviral drug development. To uncover critical pathways and potential targets of influenza infection, we assembled a large amount of data from 8 RNA sequencing studies of IAV infection for integrative network analysis. Weighted gene co-expression network analysis (WGCNA) was performed to investigate modules and genes correlated with the time course of infection and/or multiplicity of infection (MOI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and pathways of the genes in 5 significant modules. Top hub genes were identified using the cytoHubba plugin in the protein interaction network. The correlation between expression levels of 7 top hub genes and time course or MOI was displayed and validated, including BCL2L13, PLSCR1, ARID5A, LMO2, NDRG4, HAP1, and CARD10. Dysregulated expression of these genes potently impacted the development of IAV infection through modulating IAV-related biological processes and pathways. This study provides further insights into the underlying molecular mechanisms and potential targets in IAV infection.

show abstract

Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip

Cited by 57 publications

References 84 publications

Breakthroughs and Applications of Organ-on-a-Chip Technology

Breakthroughs and Applications of Organ-on-a-Chip Technology

3D Lung Tissue Models for Studies on SARS-CoV-2 Pathophysiology and Therapeutics

Identification of Critical Genes and Pathways for Influenza A Virus Infections via Bioinformatics Analysis

Contact Info

Product

Resources

About