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Cited by 68Vector-borne infectious diseasesMicrobial infections and disease researchBacterial Genetics and Biotechnology

Rapid Activation of Protein Tyrosine Kinase and Phospholipase C-γ2 and Increase in Cytosolic Free Calcium Are Required by Ehrlichia chaffeensis for Internalization and Growth in THP-1 Cells

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Lin, Mingqun, Zhu, Michael X., Rikihisa, Yasuko·2002·Infection and Immunity
DOI 10.1128/iai.70.2.889-898.2002PMC PMC127685
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Abstract

Ehrlichia chaffeensis, a bacterium that cannot survive outside the eukaryotic cell, proliferates exclusively in human monocytes and macrophages. In this study, signaling events required for ehrlichial infection of human monocytic cell line THP-1 were characterized. Entry and proliferation of E. chaffeensis in THP-1 cells were significantly blocked by various inhibitors that can regulate calcium signaling, including 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate and 2-aminoethoxydiphenyl borate (intracellular calcium mobilization inhibitors), verapamil and 1-{β-[3-(4-methoxyphenyl)propyl]-4-methoxyphenethyl}-1H-imidazole (SKF-96365) (calcium channel inhibitors), neomycin and 1-(6-{[17β-3-methoxyestra-1,3,5(10)-trien-17-yl]amino}hexyl)-1H-pyrrole-2,5-dione (U-73122) (phospholipase C [PLC] inhibitors), monodansylcadaverine (a transglutaminase [TGase] inhibitor), and genistein (a protein tyrosine kinase [PTK] inhibitor). Addition of E. chaffeensis resulted in rapid increases in the level of inositol 1,4,5-trisphosphate (IP 3) and the level of cytosolic free calcium ([Ca 2+]i) in THP-1 cells, which were prevented by pretreatment of THP-1 cells with inhibitors of TGase, PTK, and PLC.E. chaffeensis induced rapid tyrosine phosphorylation of PLC-γ2, and the presence of a PLC-γ2 antisense oligonucleotide in THP-1 cells significantly blocked ehrlichial infection. Furthermore, tyrosine-phosphorylated proteins and PLC-γ2 were colocalized with ehrlichial inclusions, as determined by double-immunofluorescence labeling. The heat-sensitive component of viable E. chaffeensis cells was essential for these signaling events.E. chaffeensis, therefore, can recruit interacting signal-transducing molecules and induce the following signaling events required for the establishment of infection in host cells: protein cross-linking by TGase, tyrosine phosphorylation, PLC-γ2 activation, IP 3 production, and an increase in [Ca 2+]i.

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  • PLCγ2 can be exploited by intracellular bacteria such as Ehrlichia chaffeensis, where recruitment and activation of PLCγ2 is required to maintain stable calcium levels to facilitate intracellular infections.

    “PLCγ2 can also be exploited by some intracellular bacteria, such as Ehrlichia chaffeensis in the monocytic THP-1 cell line, where the recruitment and activation of PLCγ2 is required to maintain stable calcium levels to facilitate intracellular infections (82).”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [82]

    The Results report that E. chaffeensis recruits and activates PLC-γ2 in THP-1 cells and that PLC-γ2 is required for infection. They do not support the claim that this maintains stable calcium levels: the Results say calcium rose rapidly in individual cells, then returned to baseline within four minutes (page numbers unavailable). (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Lin, M., Zhu, M. X., & Rikihisa, Y.
Affiliations
  • The Ohio State University (US)
  • Department of Veterinary Biosciences
Corresponding author
Rikihisa, Yasuko
ORCID
Venue
Infection and Immunity
Publisher
American Society for Microbiology
Published
2002-02
Volume
70
Issue
2
Pages
889-898
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
DOI
10.1128/iai.70.2.889-898.2002
PMC
PMC127685
OpenAlex
W2139262051
Cited by
68
References
0
Citations by year
2026: 2 · 2025: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 3 · 2013: 4 · 2012: 3
FWCI
3.16
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Infection and Immunity (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ai040934-05)
  • National Institute of Allergy and Infectious Diseases (R01AI030010, R01AI40934, R01 AI30010)
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
  • Life Sciences › Immunology and Microbiology › Microbiology › Microbial infections and disease research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
Ehrlichia chaffeensis, THP-1 cells, host cell signaling, tyrosine kinase, PLCγ2, cytosolic free calcium, inositol 1,4,5-trisphosphate, transglutaminase, tyrosine phosphorylation, host-pathogen interaction
MeSH terms
Calcium, Cell Line, Cytosol, Endocytosis, Enzyme Activation, Humans, Isoenzymes, Type C Phospholipases, Phosphorylation, Protein-Tyrosine Kinases, Time Factors, Tyrosine, Inositol 1,4,5-Trisphosphate, Ehrlichia chaffeensis, Calcium Signaling, Phospholipase C gamma

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