The Liu Cuihua team from the Institute of Microbiology, Chinese Academy of Sciences and the Pang Yu team from Beijing Chest Hospital have discovered a new innate immune mechanism for tuberculosis resistant populations to resist Mycobacterium tuberculosis infection

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
.

The Liu Cuihua team of the Institute of Microbiology, Chinese Academy of Sciences has long been committed to studying the molecular mechanisms of the interaction between Mtb and other important pathogens and the host.
In recent years, it has been published in Autophagy (2021), EMBO Report (2021), Nature Communications (2019, 2017) and Nature Immunology (2015) A series of research work published in other journals has achieved important results in the interaction mechanism between pathogens and hosts, providing 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 healthy individuals who have been in close contact with pathogens for a long time are called TB resisters
.

At present, little is known about the anti-infection and immune mechanism of such TB resistant persons.
In-depth revealing of the relevant mechanisms is expected to provide new clues and new strategies for the prevention and treatment of TB
.

Recently, Liu Cuihua’s team from the Institute of Microbiology and Professor Pang Yu’s team from Beijing Chest Hospital Affiliated to Capital Medical University revealed 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 infections 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 maintains 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 autophagyflux (autophagyflux) 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 1)
.

Figure 1.
The innate immune mechanism of people with natural tuberculosis resistance relying on HDAC6 to resist Mycobacterium tuberculosis infection.
At present, relevant results have been published online in The FASEB Journal, entitled "HDAC6 contributes to human resistance against Mycobacterium tuberculosis infection via mediatinginnate immune responses"
.

Doctoral students Zhang Fuzhen and Yu Shanshan (both visiting graduate students of the Institute of Microbiology of the Chinese Academy of Sciences) of Professor Pang Yu’s team, as well as special research assistant Chai Qiyao of Liu Cuihua’s group and project researcher Wang Jing are the co-first authors of this 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
.

Article link: https://faseb.
onlinelibrary.
wiley.
com/doi/full/10.
1096/fj.
202100614R