Tags

Type your tag names separated by a space and hit enter

Endosomal toll-like receptors play a key role in activation of primary human monocytes by cowpea mosaic virus.

Abstract

The plant virus, cowpea mosaic virus (CPMV), has demonstrated a remarkable capacity to induce anti-tumour immune responses following direct administration into solid tumours. The molecular pathways that account for these effects and the capacity of CPMV to activate human cells are not well defined. Here, we examine the ability of CPMV particles to activate human monocytes, dendritic cells (DCs) and macrophages. Monocytes in peripheral blood mononuclear cell cultures and purified CD14+ monocytes were readily activated by CPMV in vitro, leading to induction of HLA-DR, CD86, PD-L1, IL-15R and CXCL10 expression. Monocytes released chemokines, CXCL10, MIP-1α and MIP-1β into cell culture supernatants after incubation with CPMV. DC subsets (pDC and mDC) and monocyte-derived macrophages also demonstrated evidence of activation after incubation with CPMV. Inhibitors of spleen tyrosine kinase (SYK), endocytosis or endocytic acidification impaired the capacity of CPMV to activate monocytes. Furthermore, CPMV activation of monocytes was partially blocked by a TLR7/8 antagonist. These data demonstrate that CPMV activates human monocytes in a manner dependent on SYK signalling, endosomal acidification and with an important contribution from TLR7/8 recognition.

Authors+Show Affiliations

Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA. Department of Medical Laboratory Technology, College of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia.Department of Biomedical Engineering, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, NH, USA.Department of NanoEngineering, University of California San Diego, La Jolla, CA, USA. Department of Radiology, University of California San Diego, La Jolla, CA, USA. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.Division of Infectious Diseases and HIV Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31630392

Citation

Albakri, Marwah M., et al. "Endosomal Toll-like Receptors Play a Key Role in Activation of Primary Human Monocytes By Cowpea Mosaic Virus." Immunology, 2019.
Albakri MM, Veliz FA, Fiering SN, et al. Endosomal toll-like receptors play a key role in activation of primary human monocytes by cowpea mosaic virus. Immunology. 2019.
Albakri, M. M., Veliz, F. A., Fiering, S. N., Steinmetz, N. F., & Sieg, S. F. (2019). Endosomal toll-like receptors play a key role in activation of primary human monocytes by cowpea mosaic virus. Immunology, doi:10.1111/imm.13135.
Albakri MM, et al. Endosomal Toll-like Receptors Play a Key Role in Activation of Primary Human Monocytes By Cowpea Mosaic Virus. Immunology. 2019 Oct 20; PubMed PMID: 31630392.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endosomal toll-like receptors play a key role in activation of primary human monocytes by cowpea mosaic virus. AU - Albakri,Marwah M, AU - Veliz,Frank A, AU - Fiering,Steven N, AU - Steinmetz,Nicole F, AU - Sieg,Scott F, Y1 - 2019/10/20/ PY - 2019/05/31/received PY - 2019/09/20/revised PY - 2019/10/14/accepted PY - 2019/10/21/pubmed PY - 2019/10/21/medline PY - 2019/10/21/entrez KW - Syk signalling KW - TLR7/8 KW - cowpea mosaic virus KW - endosome inhibitor KW - monocytes JF - Immunology JO - Immunology N2 - The plant virus, cowpea mosaic virus (CPMV), has demonstrated a remarkable capacity to induce anti-tumour immune responses following direct administration into solid tumours. The molecular pathways that account for these effects and the capacity of CPMV to activate human cells are not well defined. Here, we examine the ability of CPMV particles to activate human monocytes, dendritic cells (DCs) and macrophages. Monocytes in peripheral blood mononuclear cell cultures and purified CD14+ monocytes were readily activated by CPMV in vitro, leading to induction of HLA-DR, CD86, PD-L1, IL-15R and CXCL10 expression. Monocytes released chemokines, CXCL10, MIP-1α and MIP-1β into cell culture supernatants after incubation with CPMV. DC subsets (pDC and mDC) and monocyte-derived macrophages also demonstrated evidence of activation after incubation with CPMV. Inhibitors of spleen tyrosine kinase (SYK), endocytosis or endocytic acidification impaired the capacity of CPMV to activate monocytes. Furthermore, CPMV activation of monocytes was partially blocked by a TLR7/8 antagonist. These data demonstrate that CPMV activates human monocytes in a manner dependent on SYK signalling, endosomal acidification and with an important contribution from TLR7/8 recognition. SN - 1365-2567 UR - https://www.unboundmedicine.com/medline/citation/31630392/Endosomal_toll-like_receptors_play_a_key_role_in_activation_of_primary_human_monocytes_by_Cowpea_Mosaic_Virus L2 - https://doi.org/10.1111/imm.13135 DB - PRIME DP - Unbound Medicine ER -