Mycobacterium tuberculosis Utilizes Host Histamine Receptor H1 to Modulate Reactive Oxygen Species Production and Phagosome Maturation via the p38MAPK-NOX2 Axis

Mo, Siwei1,6,7; Guo, Jiubiao2; Ye, Taosheng3; Zhang, Ximeng1; Zeng, Jiang4; Xu, Yuzhong5; Bin Peng1; Dai, Youchao1; Xiao, Wei1; Zhang, Peize3; Deng, Guofang3; Xu, Dechang4; Long, Xiaoru6,7; Cai, Yi1; Chen, Xinchun1

2022-08-01

10.1128/mbio.02004-22

mBio   Impact Factor & Quartile

2150-7511

["Once engulfed in macrophage phagosomes, M. tuberculosis adopts various strategies to take advantage of the host environment for its intracellular survival. Histamine is an organic nitrogen-containing compound that mediates a plethora of cellular processes via different receptors, but the crosstalk mechanism between M. tuberculosis and HRH1 in macrophages is not clear.","Tuberculosis (TB), which is caused by the single pathogenic bacterium, Mycobacterium tuberculosis, is among the top 10 lethal diseases worldwide. This situation has been exacerbated by the increasing number of cases of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Histamine is an organic nitrogenous compound that mediates a plethora of cell processes via different receptors. The expression of histamine receptor H1 (HRH1), one of the four histamine receptors identified to date was previously reported to be augmented by M. tuberculosis infection, although the underlying mechanism is unclear. In the present study, we applied confocal microscopy, flow cytometry, and Western blotting to show that HRH1 expression was enhanced in macrophages following mycobacterial infection. Furthermore, by combining techniques of gene knockdown, immunoprecipitation, intracellular bacterial burden analysis, fluorescence labeling, and imaging, we found that M. tuberculosis targeted the host HRH1 to suppress NOX2-mediated cROS production and inhibit phagosome maturation and acidification via the GRK2-p38MAPK signaling pathway. Our findings clarified the underlying mechanism of the M. tuberculosis and host HRH1 interaction and may provide useful information for the development of novel antituberculosis treatments. IMPORTANCE Once engulfed in macrophage phagosomes, M. tuberculosis adopts various strategies to take advantage of the host environment for its intracellular survival. Histamine is an organic nitrogen-containing compound that mediates a plethora of cellular processes via different receptors, but the crosstalk mechanism between M. tuberculosis and HRH1 in macrophages is not clear. Our results revealed that M. tuberculosis infection enhanced HRH1 expression, which in turn restrained macrophage bactericidal activity by modulating the GRK2-p38MAPK signaling pathway, inhibiting NOX2-mediated cROS production and phagosome maturation. Clarification of the underlying mechanism by which M. tuberculosis utilizes host HRH1 to favor its intracellular survival may provide useful information for the development of novel antituberculosis treatments."]

Mycobacterium tuberculosis HRH1 NOX2 p38MAPK ROS

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National Natural Science Foundation of China["82130066","82072252","31800064","82070016"] ; Science and Technology Project of Shenzhen["JCYJ20200109105012589","JCYJ20180507182049853"] ; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases[2019B030301009] ; Natural Science Foundation of Top Talent of SZTU[GDRC202120] ; Natural Science Foundation of Chongqing City[cstc2020jcyj-msxmX0580] ; general project of clinical medicine research of National Center for clinical medicine of child health and disease[NCRCCHD-2020-GP-06]

Microbiology

Microbiology

WOS:000844488700001

AMER SOC MICROBIOLOGY

Web of Science

1.Shenzhen Univ, Dept Pathogen Biol, Guangdong Prov Key Lab Reg Immun & Dis, Sch Med, Shenzhen, Peoples R China
2.Shenzhen Technol Univ, Coll Pharm, Shenzhen, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis Shenzhen, Pulm Dis Dept 2,Guangdong Prov Clin Res Ctr Inf, Shenzhen, Peoples R China
4.Fifth Peoples Hosp Ganzhou, Ganzhou, Jiangxi, Peoples R China
5.Shenzhen Univ, Dept Clin Lab, Shenzhen Baoan Hosp, Shenzhen, Peoples R China
6.Chongqing Med Univ, Dept Resp Med, Chongqing Key Lab Pediat, Childrens Hosp, Chongqing, Peoples R China
7.Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders,Chongqin, Minist Educ,Key Lab Child Dev & Disorders,China I, Chongqing, Peoples R China

Mo, Siwei,Guo, Jiubiao,Ye, Taosheng,et al. Mycobacterium tuberculosis Utilizes Host Histamine Receptor H1 to Modulate Reactive Oxygen Species Production and Phagosome Maturation via the p38MAPK-NOX2 Axis[J]. mBio,2022.

Mo, Siwei.,Guo, Jiubiao.,Ye, Taosheng.,Zhang, Ximeng.,Zeng, Jiang.,...&Chen, Xinchun.(2022).Mycobacterium tuberculosis Utilizes Host Histamine Receptor H1 to Modulate Reactive Oxygen Species Production and Phagosome Maturation via the p38MAPK-NOX2 Axis.mBio.

Mo, Siwei,et al."Mycobacterium tuberculosis Utilizes Host Histamine Receptor H1 to Modulate Reactive Oxygen Species Production and Phagosome Maturation via the p38MAPK-NOX2 Axis".mBio (2022).