1. P-type pilus PapG protein elicits toll-like receptor 2-mediated immune activation during cancer immunotherapy.
- Author
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Zhang W, Park HB, Yadav D, An EK, Kim SJ, Ryu D, Agrawal R, Ryu JH, Kwak M, Lee PCW, and Jin JO
- Subjects
- Animals, Mice, Humans, Melanoma, Experimental immunology, Melanoma, Experimental therapy, Melanoma, Experimental pathology, Fimbriae Proteins immunology, Mice, Inbred C57BL, Lymphocyte Activation drug effects, Fimbriae, Bacterial immunology, Cytokines metabolism, Cell Proliferation drug effects, T-Lymphocytes immunology, Toll-Like Receptor 2 metabolism, Immunotherapy methods, Dendritic Cells immunology
- Abstract
The immune activation ability of FimH, an adhesion protein in pili of Escherichia coli (E. coli), has been recently reported. However, studies on the immune activity of PapG, another major pili terminal protein, have not been well explored. In this study, the immune stimulatory effect of purified recombinant PapG was evaluated. PapG treatment promoted dramatic changes in dendritic morphology of the bone marrow-derived dendritic cells (BMDCs) and induced upregulation of co-stimulatory molecule levels, major histocompatibility complex (MHC) I and II expression, and pro-inflammatory cytokine production in BMDCs. To identify the stimulatory receptor of PapG, an in silico study was performed. PapG exhibited strong binding affinity with murine toll-like receptor 2 (TLR2). In addition, PapG-induced activation of splenic DC and its subsets was unsuccessful in TLR2-knock out mice. Combination of PapG and ovalbumin (OVA) elicited OVA-specific T cell proliferation and cytokine production and cytotoxicity that consequently promoted anti-cancer immune responses against OVA-expressing B16 melanoma. Furthermore, PapG treatment induced activation of peripheral blood DCs and its subsets in humans in a TLR2 dependent manner. PapG-stimulated human conventional DC2 promoted syngeneic T cell proliferation and activation. The findings of this study demonstrated that PapG could be a useful immune stimulator for immunotherapy against cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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