Tuberculosis (TB), a contagious disease caused by Mycobacterium tuberculosis (Mtb), remains a major cause of morbidity and mortality worldwide. Dr. Liu Cuihua’s group has been investigating the molecular mechanisms underlying Mtb-host interplays, and previous studies from her group have provided potential targets for the development of anti-TB treatments based on pathogen-host interacting interfaces (Autophagy, 2021; EMBO Report, 2021; Nature Communications, 2019; Nature Communications, 2017; Nature Immunology, 2015).

Increasing lines of evidence indicate that some individuals, termed resisters, are naturally resistant to TB infection. The resister phenotype has been linked to efficient host innate immune responses, but the underlying mechanisms and the key immune factors remain poorly understood. Recently, Dr. Liu’s group, in collaboration with Dr. Yu Pang’s group from Beijing Chest Hospital, found that histone deacetylase 6 (HDAC6) is persistently expressed in monocyte-derived macrophages from resisters during Mtb infection. They further showed that HDAC6 acts as a key host factor required for macrophage production by pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, and acidification of Mtb-containing vacuoles for bacterial clearance. Taken together, this study’s results reveal an indispensable role of HDAC6 in mediating anti-Mtb innate immune responses in resisters, and imply that HDAC6 may serve as a marker for individual TB risk as well as a novel host-directed anti-TB therapeutic target.

The paper, entitled “HDAC6 contributes to human resistance against Mycobacterium tuberculosis infection via mediating innate immune responses”, has been published online in The FASEB Journal with Zhang Fuzhen, Yu Shanshan, Chai Qiyao and Wang Jing as the co-first authors and Dr. Liu and Dr. Yu as the co-corresponding authors.

Schematic model showing mechanisms by which resisters display enhanced innate immune responses against Mycobacterium tuberculosis infection [image: CAS Key Laboratory of Pathogenic Microbiology and Immunology]

For more information, please contact:

Dr. Liu Cuihua

E-mail: liucuihua@im.ac.cn

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology,

Chinese Academy of Sciences

Source: CAS Key Laboratory of Pathogenic Microbiology and Immunology,

Institute of Microbiology,

Chinese Academy of Sciences