scholarly journals Erratum: “Human lung-on-chips: Advanced systems for respiratory virus models and assessment of immune response” [Biomicrofluidics 15, 021501 (2021)]

2021 ◽  
Vol 15 (3) ◽  
pp. 039901
Author(s):  
Ecem Saygili ◽  
Ece Yildiz-Ozturk ◽  
Macauley J. Green ◽  
Amir M. Ghaemmaghami ◽  
Ozlem Yesil-Celiktas
Keyword(s):  
Immune Response ◽  
Respiratory Virus ◽  
Human Lung

Human lung-on-chips: Advanced systems for respiratory virus models and assessment of immune response

2021 ◽  
Vol 15 (2) ◽  
pp. 021501
Author(s):  
Ecem Saygili ◽  
Ece Yildiz-Ozturk ◽  
Macauley J. Green ◽  
Amir M. Ghaemmaghami ◽  
Ozlem Yesil-Celiktas
Keyword(s):  
Immune Response ◽  
Respiratory Virus ◽  
Human Lung

scholarly journals Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19

2020 ◽  
Author(s):  
Courtney Tindle ◽  
MacKenzie Fuller ◽  
Ayden Fonseca ◽  
Sahar Taheri ◽  
Stella-Rita Ibeawuchi ◽  
...  
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
Host Response ◽  
Human Lung ◽  
Adult Stem Cell ◽  
Lung Model ◽  
Alveolar Type ◽  
List Type ◽  
Alveolar Cells ◽  
Airway Cells

SummarySARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19. Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection, whereas distal alveolar differentiation (AT2→AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both. Findings validate a human lung model of COVID-19, which can be immediately utilized to investigate COVID-19 pathogenesis and vet new therapies and vaccines.GRAPHIC ABSTRACTHIGHLIGHTSHuman lung organoids with mixed proximodistal epithelia are createdProximal airway cells are critical for viral infectivityDistal alveolar cells are important for emulating host responseBoth are required for the overzealous response in severe COVID-19IN BRIEFAn integrated stem cell-based disease modeling and computational approach demonstrate how both proximal airway epithelium is critical for SARS-CoV-2 infectivity, but distal differentiation of alveolar pneumocytes is critical for simulating the overzealous host response in fatal COVID-19.

scholarly journals Authentic Modeling of Human Respiratory Virus Infection in Human Pluripotent Stem Cell-Derived Lung Organoids

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
M. Porotto ◽  
M. Ferren ◽  
Y.-W. Chen ◽  
Y. Siu ◽  
N. Makhsous ◽  
...  
Keyword(s):  
Virus Infection ◽  
Viral Infection ◽  
Pluripotent Stem Cells ◽  
Respiratory Virus ◽  
Human Lung ◽  
Cultured Cells ◽  
Virus Infections ◽  
Distal Lung ◽  
Syncytial Virus ◽  
Respiratory Virus Infections

ABSTRACTInfectious viruses so precisely fit their hosts that the study of natural viral infection depends on host-specific mechanisms that affect viral infection. For human parainfluenza virus 3, a prevalent cause of lower respiratory tract disease in infants, circulating human viruses are genetically different from viruses grown in standard laboratory conditions; the surface glycoproteins that mediate host cell entry on circulating viruses are suited to the environment of the human lung and differ from those of viruses grown in cultured cells. Polarized human airway epithelium cultures have been used to represent the large, proximal airways of mature adult airways. Here we modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids derived from human pluripotent stem cells contain mesoderm and pulmonary endoderm and develop into branching airway and alveolar structures. Whole-genome sequencing analysis of parainfluenza viruses replicating in the organoids showed maintenance of nucleotide identity, suggesting that no selective pressure is exerted on the virus in this tissue. Infection with parainfluenza virus led to viral shedding without morphological changes, while respiratory syncytial virus infection induced detachment and shedding of infected cells into the lung organoid lumens, reminiscent of parainfluenza and respiratory syncytial virus in human infant lungs. Measles virus infection, in contrast, induced syncytium formation. These human stem cell-derived lung organoids may serve as an authentic model for respiratory viral pathogenesis in the developing or infant lung, recapitulating respiratory viral infection in the host.IMPORTANCERespiratory viruses are among the first pathogens encountered by young children, and the significant impact of these viral infections on the developing lung is poorly understood. Circulating viruses are suited to the environment of the human lung and are different from those of viruses grown in cultured cells. We modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids, derived from human pluripotent stem cells, develop into branching airway and alveolar structures and provide a tissue environment that maintains the authentic viral genome. The lung organoids can be genetically engineered prior to differentiation, thereby generating tissues bearing or lacking specific features that may be relevant to viral infection, a feature that may have utility for the study of host-pathogen interaction for a range of lung pathogens.

Immune Response to Peptides Produced by Enzymatic Digestion of Microfibrils And Elastin of Human Lung Parenchyma

1977 ◽  
Vol 5 (2) ◽  
pp. 67-73 ◽  
Author(s):  
Tukaram V. Darnule ◽  
Vinay Likhite ◽  
Gerard M. Turino ◽  
Ines Mandl
Keyword(s):  
Immune Response ◽  
Human Lung ◽  
Lung Parenchyma ◽  
Enzymatic Digestion

Degradation-regulated architecture of injectable smart hydrogels enhances humoral immune response and potentiates antitumor activity in human lung carcinoma

Biomaterials ◽  
2020 ◽  
Vol 230 ◽  
pp. 119599 ◽  
Author(s):  
Huu Thuy Trang Duong ◽  
Thavasyappan Thambi ◽  
Yue Yin ◽  
Seong Han Kim ◽  
Thanh Loc Nguyen ◽  
...  
Keyword(s):  
Immune Response ◽  
Antitumor Activity ◽  
Lung Carcinoma ◽  
Humoral Immune Response ◽  
Human Lung ◽  
Humoral Immune ◽  
Human Lung Carcinoma

scholarly journals Human Lung Innate Immune Response to Bacillus anthracis Spore Infection

2007 ◽  
Vol 75 (8) ◽  
pp. 3729-3738 ◽  
Author(s):  
Kaushik Chakrabarty ◽  
Wenxin Wu ◽  
J. Leland Booth ◽  
Elizabeth S. Duggan ◽  
Nancy N. Nagle ◽  
...  
Keyword(s):  
Immune Response ◽  
Bacillus Anthracis ◽  
Innate Immune Response ◽  
Human Lung ◽  
Rnase Protection Assay ◽  
Innate Immune ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rnase Protection ◽  
Cell Signal ◽  
Cytokines And Chemokines

ABSTRACT Bacillus anthracis, the causative agent of inhalational anthrax, enters a host through the pulmonary system before dissemination. We have previously shown that human alveolar macrophages participate in the initial innate immune response to B. anthracis spores through cell signal-mediated cytokine release. We proposed that the lung epithelia also participate in the innate immune response to this pathogen, and we have developed a human lung slice model to study this process. Exposure of our model to B. anthracis (Sterne) spores rapidly activated the mitogen-activated protein kinase signaling pathways ERK, p38, and JNK. In addition, an RNase protection assay showed induction of mRNA of several cytokines and chemokines. This finding was reflected at the translational level by protein peak increases of 3-, 25-, 9-, 34-, and 5-fold for interleukin-6 (IL-6), tumor necrosis factor alpha, IL-8, macrophage inflammatory protein 1α/β, and monocyte chemoattractant protein 1, respectively, as determined by an enzyme-linked immunosorbent assay. Inhibition of individual pathways by UO126, SP600125, and SB0203580 decreased induction of chemokines and cytokines by spores, but this depended on the pathways inhibited and the cytokines and chemokines induced. Combining all three inhibitors reduced induction of all cytokines and chemokines tested to background levels. An immunohistochemistry analysis of IL-6 and IL-8 revealed that alveolar epithelial cells and macrophages and a few interstitial cells are the source of the cytokines and chemokines. Taken together, these data showed the activation of the pulmonary epithelium in response to B. anthracis spore exposure. Thus, the lung epithelia actively participate in the innate immune response to B. anthracis infection through cell signal-mediated elaboration of cytokines and chemokines.

scholarly journals Detection of Antibody Responses Against SARS-CoV-2 in Plasma and Saliva From Vaccinated and Infected Individuals

2021 ◽  
Vol 12 ◽  
Author(s):  
Jéromine Klingler ◽  
Gregory S. Lambert ◽  
Vincenza Itri ◽  
Sean Liu ◽  
Juan C. Bandres ◽  
...  
Keyword(s):  
Immune Response ◽  
Specific Antibody ◽  
Strong Correlation ◽  
Respiratory Virus ◽  
Host Immune Response ◽  
Antibody Responses ◽  
Lower Prevalence ◽  
Antiviral Activities ◽  
Virus Exposure ◽  
Complement Deposition

Antibodies (Abs) are essential for the host immune response against SARS-CoV-2, and all the vaccines developed so far have been designed to induce Abs targeting the SARS-CoV-2 spike. Many studies have examined Ab responses in the blood from vaccinated and infected individuals. However, since SARS-CoV-2 is a respiratory virus, it is also critical to understand the mucosal Ab responses at the sites of initial virus exposure. Here, we examined plasma versus saliva Ab responses in vaccinated and convalescent patients. Although saliva levels were significantly lower, a strong correlation was observed between plasma and saliva total Ig levels against all SARS-CoV-2 antigens tested. Virus-specific IgG1 responses predominated in both saliva and plasma, while a lower prevalence of IgM and IgA1 Abs was observed in saliva. Antiviral activities of plasma Abs were also studied. Neutralization titers against the initial WA1 (D614G), B.1.1.7 (alpha) and B.1.617.2 (delta) strains were similar but lower against the B.1.351 (beta) strain. Spike-specific antibody-dependent cellular phagocytosis (ADCP) activities were also detected and the levels correlated with spike-binding Ig titers. Interestingly, while neutralization and ADCP potencies of vaccinated and convalescent groups were comparable, enhanced complement deposition to spike-specific Abs was noted in vaccinated versus convalescent groups and corresponded with higher levels of IgG1 plus IgG3 among the vaccinated individuals. Altogether, this study demonstrates the detection of Ab responses after vaccination or infection in plasma and saliva that correlate significantly, although Ig isotypic differences were noted. The induced plasma Abs displayed Fab-mediated and Fc-dependent functions with comparable neutralization and ADCP potencies, but a greater capacity to activate complement was elicited upon vaccination.

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