January 26, 2023

Hunting for the Immune Cells That Lead to Severe COVID-19

Why some people, and not others, establish really severe disease has been a mystery,” stated Asst. Prof. Huanhuan Joyce Chen, who led the research study with Qizhou Lian of the University of Hong Kong. The brand-new findings from the Joyce Chen Lab might notify the avoidance or treatment of severe COVID-19 in the most at-risk patients. Above, Asst. Prof. Chen works with postdoctoral scientists Abhimanyu Thakur (left) and Kui Zhang (right). To much better comprehend the function of macrophages throughout a COVID-19 infection, Chens team developed an approach that might make use of the exact same line of human stem cells to become both lung cells and macrophages all at once. And Chen is currently thinking ahead to her next experiments with the stem cell-derived organoids.

Asst. Prof. Huanhuan Joyce Chen of Pritzker Molecular Engineering led a new research study showing that the kind of macrophages present in a persons body may identify how likely they are to establish severe inflammation in reaction to COVID-19. Credit: Photo by John Zich
University of Chicago Pritzker School of Molecular Engineering scientists indicate macrophages.
When an infection makes its method into a persons body, among the immune systems first responders is a set of pathogen-removal cells called macrophages. However macrophages are varied; they dont all target infections in the same method.
Researchers at the University of Chicagos Pritzker School of Molecular Engineering have discovered that the kind of macrophages present in an individuals body might figure out how likely they are to establish extreme inflammation in response to COVID-19. Their research study was released recently in the journal Nature Communications.

” Clinicians know that COVID-19 can cause a spectrum of disease intensity from mild to serious signs. Why some people, and not others, develop extremely serious illness has actually been a secret,” stated Asst. Prof. Huanhuan Joyce Chen, who led the research study with Qizhou Lian of the University of Hong Kong. “This is the first time anybody has actually connected the variation in signs to macrophages.”
A much better model for COVID-19 infection
Studying the molecular and cellular results of the SARS-CoV-2 infection has been challenging for researchers who typically turn to design organisms to mimic human illness, due to the fact that mice, rats, and numerous other animals dont develop the exact same COVID-19 symptoms as people. Thats why, shortly after the COVID-19 pandemic started, Joyce Chen Lab utilized human stem cells to study the infection.
The new findings from the Joyce Chen Lab could notify the prevention or treatment of serious COVID-19 in the most at-risk patients. Above, Asst. Prof. Chen deals with postdoctoral researchers Abhimanyu Thakur (left) and Kui Zhang (ideal). Credit: Photo by John Zich
As reported previously in Nature, Chen and her associates grew stem cells into operating mini-lungs and colons– called lung and colon organoids– to probe the results of SARS-CoV-2 on those organs and screen drugs to deal with the virus.
In the new study, the researchers first evaluated lung biopsies from COVID-19 patients and discovered that they had specifically high levels of macrophages. To better understand the role of macrophages throughout a COVID-19 infection, Chens team established a technique that could exploit the same line of human stem cells to become both lung cells and macrophages concurrently. The fact that they developed from the exact same initial stem cells was crucial to prevent the immune cells from assaulting the lung cells.
” This design system provides an ideal way to decode, step by step, how these three components– the immune system, the lungs, and the virus– engage,” said Chen.
A cascade of swelling
When Chens laboratory infected the stem cell-derived lungs and macrophages with SARS-CoV-2, they discovered that not all macrophages reacted in the very same method. One subset, called M2 macrophages, eliminate the virus by physically engulfing virus and virus-infected cells in a procedure known as phagocytosis, while releasing anti-inflammatory molecules.
M1 macrophages acted in an opposite method: these cells launched a huge selection of inflammatory chemical signals that not only battle SARS-CoV-2, however trigger a more widespread immune reaction. These same inflammatory elements have actually been shown to be present in the blood of people with serious COVID-19 symptoms.
Asst. Prof. Chen, here dealing with graduate student Jingwen Xu, examined the effects of SARS-CoV-2 on lung and colon organoids in a previous research study. Credit: Photo by John Zich
” Our results suggest that people who currently have actually M1 macrophages activated in the lungs when contaminated with COVID-19 may be more most likely to develop really serious inflammation from the virus,” said Chen.
Elderly people and those with particular conditions like high blood pressure or diabetes– currently understood to be prone to more severe COVID-19 symptoms– might have greater levels of the M1 macrophages, she added.
Her team went on to reveal that antibodies– comparable to those already utilized medically to treat COVID-19– helped M2 macrophages clear the SARS-CoV-2 virus. More work is required to reveal whether the observations are true in human beings, however the findings might assist inform the avoidance or treatment of severe COVID-19 in the most at-risk clients. And Chen is already planning ahead to her next explores the stem cell-derived organoids.
” This model system is helpful for deciphering the molecular mechanisms behind not just COVID-19, but other transmittable diseases,” said Chen.
In the future, her group wishes to make more complex mini-organs that consist of not just lung and immune cells, however capillary, nerves, and other supporting cell types.
Reference: “Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived design” by Qizhou Lian, Kui Zhang, Zhao Zhang, Fuyu Duan, Liyan Guo, Weiren Luo, Bobo Wing-Yee Mok, Abhimanyu Thakur, Xiaoshan Ke, Pedram Motallebnejad, Vlad Nicolaescu, Jonathan Chen, Chui Yan Ma, Xiaoya Zhou, Shuo Han, Teng Han, Wei Zhang, Adrian Y. Tan, Tuo Zhang, Xing Wang, Dong Xu, Jenny Xiang, Aimin Xu, Can Liao, Fang-Ping Huang, Ya-Wen Chen, Jie Na, Glenn Randall, Hung-fat Tse, Zhiwei Chen, Yin Chen and Huanhuan Joyce Chen, 19 April 2022, Nature Communications.DOI: 10.1038/ s41467-022-29731-5.
Funding: National Institute of Health, Cancer Research Foundation Young Investigator Award, Janet D. Rowley Discovery Fund, Hong Kong Health and Medical Research Fund, Guangzhou Women and Childrens Medical Centre, Shenzhen Science and Technology Program, Tsinghua University Spring Breeze Fund, the National Key R&D Program of China and the National Natural Science Grant of China.

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