Tuberculosis ( tuberculosis , TB ) is a major infectious disease caused by Mycobacterium tuberculosis ( M.
tuberculosis , Mtb )
According to the latest report released by the WHO, in 2020 , there will be nearly 9.
9 million tuberculosis patients worldwide , and about 1.
51 million people will die from tuberculosis infection
Zhong Guo LIU Cui-hua Institute of Microbiology, Academy of Sciences research group devoted to researching Mtb and other important molecular mechanisms of pathogen-host interactions and, in recent years, microtubule - targeting agent ( 2021 ), EMBO Report ( 2021 ), Nature Communications ( 2019 , 2017 ) and Nature Immunology ( 2015 ) and other journals published a series of research work, achieved important results in the interaction mechanism between pathogens and hosts, and provided a variety of new ideas and potential new targets for anti-tuberculosis treatment and drug development
In the past, it was believed that when healthy individuals were infected with Mtb , they often developed into latent infections or active TB patients
Interestingly, in recent years, it has been found that some individuals who have been in close contact with TB patients have neither developed into active TB patients and showed related symptoms, nor have they shown the immunological diagnostic characteristics of latent infections
Such long-term close contact with the pathogens of healthy individuals is called TB resisters ( Resister )
At present , little is known about the anti-infection immune mechanism of such TB resistant persons, and the in-depth revealing of the relevant mechanism is expected to provide new clues and new strategies for the prevention and treatment of TB .
Recently, Liu Cuihua's research team in our institute cooperated with Professor Pang Yu's team from Beijing Chest Hospital of Capital Medical University to reveal the characteristics of the innate immune response of the TB resistant population in response to Mtb infection .
The collaborative study found that compared with the control group, latent infection and active TB patients, the peripheral blood mononuclear macrophages of TB resistant patients can produce higher levels of TNF-α and IL- when they are infected by Mtb .
1β and IL-6 and other cytokines, and its ability to eliminate intracellular pathogenic bacteria is stronger .
A series of subsequent screening and functional verification experiments showed that during Mtb infection, histone deacetylase 6 ( HDAC6 ) only maintained a stable expression level and enzyme activity in macrophages derived from TB resistance, while There was a significant decrease in the population of other experimental groups
And further inhibition or silencing of HDAC6 can inhibit the secretion of cytokines in TB- resistant macrophages and the acidification ability of vesicles containing Mtb .
These results suggest that the ability of macrophages derived from TB resisters to efficiently eliminate Mtb infection depends on HDAC6 , which may be a key host factor that promotes cytokine production and smooth autophagy flux to accelerate Mtb clearance .
In summary, the study revealed a new innate immune mechanism by which TB resistant populations rely on HDAC6 to clear Mtb infections, providing an important new indicator for TB infection and risk prediction of clinical close contacts of TB patients , and for targeting host TB Treatment provides new ideas (Figure
At present, the relevant results have been published online in The FASEB Journal , entitled "HDAC6 contributes to human resistance against Mycobacterium tuberculosis infection via mediating innate immune responses"
, Professor Yu Pang team of Zhang and Yu Shanshan true (two are Zhong Guo Academy of Sciences Institute of Microbiology, visiting graduate students), and tied for the first author of the research group LIU Cui-hua special projects and research assistants Chaiqi Yao Jing Wang, a researcher for the article , Researcher Liu Cuihua and Professor Pang Yu are the co-corresponding authors
This work was supported by the National Key Research and Development Program, the National Natural Science Foundation of China, and the "Sailing" project of Beijing Hospital Management Center
Figure 1: The innate immune mechanism of people with natural resistance to tuberculosis who rely on HDAC6 to resist Mycobacterium tuberculosis infection
Article link: https://faseb.