Monocytes complexed to platelets differentiate into functionally deficient dendritic cells.

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dc.contributor.authorSingh, Meera V
dc.contributor.authorSuwunnakorn, Sumanun
dc.contributor.authorSimpson, Sydney R
dc.contributor.authorWeber, Emily A
dc.contributor.authorSingh, Vir B
dc.contributor.authorKalinski, Pawel
dc.contributor.authorMaggirwar, Sanjay B
dc.contributor.orcidhttps://orcid.org/0000-0002-8022-5167
dc.date.accessioned2023-11-10T16:33:42Z
dc.date.available2023-11-10T16:33:42Z
dc.date.issued2021-04
dc.description.abstractIn addition to their role in hemostasis, platelets store numerous immunoregulatory molecules such as CD40L, TGFβ, β2-microglobulin, and IL-1β and release them upon activation. Previous studies indicate that activated platelets form transient complexes with monocytes, especially in HIV infected individuals and induce a proinflammatory monocyte phenotype. Because monocytes can act as precursors of dendritic cells (DCs) during infection/inflammation as well as for generation of DC-based vaccine therapies, we evaluated the impact of activated platelets on monocyte differentiation into DCs. We observed that in vitro cultured DCs derived from platelet-monocyte complexes (PMCs) exhibit reduced levels of molecules critical to DC function (CD206, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin, CD80, CD86, CCR7) and reduced antigen uptake capacity. DCs derived from PMCs also showed reduced ability to activate naïve CD4 and CD8 T cells, and secrete IL-12p70 in response to CD40L stimulation, resulting in decreased ability to promote type-1 immune responses to HIV antigens. Our results indicate that formation of complexes with activated platelets can suppress the development of functional DCs from such monocytes. Disruption of PMCs in vivo via antiplatelet drugs such as Clopidogrel/Prasugrel or the application of platelet-free monocytes for DCs generation in vitro, may be used to enhance immunization and augment the immune control of HIV.
dc.description.grantGrant Funded
dc.description.sponsorshipP50 CA159981/CA/NCI NIH HHS/United States
dc.description.sponsorshipP50 CA159981-P3/GF/NIH HHS/United States
dc.description.sponsorshipR21 AI136668/AI/NIAID NIH HHS/United States
dc.description.sponsorshipP01 CA234212-01/GF/NIH HHS/United States
dc.description.sponsorshipR01 HL128155/HL/NHLBI NIH HHS/United States
dc.description.urihttps://doi.org/10.1002/jlb.3a0620-460rr
dc.description.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/pmc7854860/
dc.identifier.citationSingh MV, Suwunnakorn S, Simpson SR, Weber EA, Singh VB, Kalinski P, Maggirwar SB. Monocytes complexed to platelets differentiate into functionally deficient dendritic cells. J Leukoc Biol. 2021 Apr;109(4):807-820. doi: 10.1002/JLB.3A0620-460RR. Epub 2020 Jul 14. PMID: 32663904; PMCID: PMC7854860.
dc.identifier.issn0741-5400
dc.identifier.other32663904
dc.identifier.urihttps://hdl.handle.net/20.500.14303/317
dc.language.isoen
dc.publisherOxford University Press
dc.relation.ispartofJournal of Leukocyte Biology
dc.rightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). http://rightsstatements.org/vocab/InC/1.0/
dc.subjectCD40L
dc.subjectHIV infection
dc.subjectimmunotherapy
dc.subjectplatelet-monocyte complexes
dc.titleMonocytes complexed to platelets differentiate into functionally deficient dendritic cells.
dc.typeArticle
local.departmentprogramDepartment of Life Sciences
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