PMID- 37855658
OWN - NLM
STAT- MEDLINE
DCOM- 20240202
LR  - 20240203
IS  - 1674-8018 (Electronic)
IS  - 1674-800X (Print)
IS  - 1674-800X (Linking)
VI  - 15
IP  - 2
DP  - 2024 Feb 1
TI  - Anthrax lethal toxin and tumor necrosis factor-alpha synergize on intestinal 
      epithelia to induce mouse death.
PG  - 135-148
LID - 10.1093/procel/pwad050 [doi]
AB  - Bacillus anthracis lethal toxin (LT) is a determinant of lethal anthrax. Its 
      function in myeloid cells is required for bacterial dissemination, and LT itself 
      can directly trigger dysfunction of the cardiovascular system. The interplay 
      between LT and the host responses is important in the pathogenesis, but our 
      knowledge on this interplay remains limited. Tumor necrosis factor-alpha (TNF-alpha) is a 
      pleiotropic pro-inflammatory cytokine induced by bacterial infections. Since LT 
      accumulates and cytokines, predominantly TNF, amass during B. anthracis 
      infection, co-treatment of TNF + LT in mice was used to mimic in vivo conditions 
      for LT to function in inflamed hosts. Bone marrow transplantation and genetically 
      engineered mice showed unexpectedly that the death of intestinal epithelial cells 
      (IECs) rather than that of hematopoietic cells led to LT + TNF-induced lethality. 
      Inhibition of p38alpha mitogen-activated protein kinase (MAPK) signaling by LT in 
      IECs promoted TNF-induced apoptosis and necroptosis of IECs, leading to 
      intestinal damage and mouse death. Consistently, p38alpha inhibition by LT enhanced 
      TNF-mediated cell death in human colon epithelial HT-29 cells. As intestinal 
      damage is one of the leading causes of lethality in anthrax patients, the IEC 
      damage caused by LT + TNF would most likely be a mechanism underneath this 
      clinical manifestation and could be a target for interventions.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of Higher 
      Education Press.
FAU - Gao, Xinhe
AU  - Gao X
AUID- ORCID: 0009-0004-4134-3306
AD  - State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty 
      of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
FAU - Teng, Teng
AU  - Teng T
AUID- ORCID: 0009-0002-7599-7231
AD  - State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty 
      of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
FAU - Liu, Yifei
AU  - Liu Y
AUID- ORCID: 0000-0002-7684-3923
AD  - State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty 
      of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
FAU - Ai, Tingting
AU  - Ai T
AD  - State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty 
      of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
FAU - Zhao, Rui
AU  - Zhao R
AD  - State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty 
      of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
FAU - Fu, Yilong
AU  - Fu Y
AUID- ORCID: 0000-0002-2880-177X
AD  - State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty 
      of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
FAU - Zhang, Peipei
AU  - Zhang P
AUID- ORCID: 0000-0001-9234-5556
AD  - State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty 
      of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
FAU - Han, Jiahuai
AU  - Han J
AUID- ORCID: 0000-0001-5592-4487
AD  - State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty 
      of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
AD  - Research Unit of Cellular Stress of CAMS, Xiang'an Hospital of Xiamen University, 
      Cancer Research Center of Xiamen University, School of Medicine, Faculty of 
      Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
AD  - Laboratory Animal Center, Faculty of Medicine and Life Sciences, Xiamen 
      University, Xiamen 361102, China.
FAU - Zhang, Yingying
AU  - Zhang Y
AUID- ORCID: 0000-0003-0936-7776
AD  - State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty 
      of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
LA  - eng
GR  - 82388201/National Natural Science Foundation of China/
GR  - 2020YFA0803500/National Key R&D Program of China/
GR  - 2019-I2M-5-062/CAMS Innovation Fund for Medical Sciences/
PT  - Journal Article
PL  - Germany
TA  - Protein Cell
JT  - Protein & cell
JID - 101532368
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Cytokines)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - Tumor Necrosis Factor-alpha
MH  - *Anthrax/microbiology/pathology
MH  - *Bacillus anthracis
MH  - Cytokines
MH  - Signal Transduction
PMC - PMC10833652
OTO - NOTNLM
OT  - TNF
OT  - cell death
OT  - intestinal epithelial cell
OT  - lethal toxin
OT  - p38alpha
COIS- All authors declare no competing interests in this paper.
EDAT- 2023/10/19 12:45
MHDA- 2024/02/02 06:42
PMCR- 2023/10/19
CRDT- 2023/10/19 09:33
PHST- 2023/08/16 00:00 [received]
PHST- 2023/09/26 00:00 [accepted]
PHST- 2024/02/02 06:42 [medline]
PHST- 2023/10/19 12:45 [pubmed]
PHST- 2023/10/19 09:33 [entrez]
PHST- 2023/10/19 00:00 [pmc-release]
AID - 7321984 [pii]
AID - pwad050 [pii]
AID - 10.1093/procel/pwad050 [doi]
PST - ppublish
SO  - Protein Cell. 2024 Feb 1;15(2):135-148. doi: 10.1093/procel/pwad050.