Neem leaf glycoprotein suppresses regulatory T cell mediated suppression of monocyte/macrophage functions.
We have shown that neem leaf glycoprotein (NLGP) inhibits the regulatory T cell (Tregs) induced suppression of tumoricidal functions of CD14(+)CD68(+) monocyte/macrophages (MO/Mφ) from human peripheral blood. Cytotoxic efficacy of MO/Mφ toward macrophage sensitive cells, U937, is decreased in presence of Tregs (induced), however, it was increased further by supplementation of NLGP in culture. Associated Treg mediated inhibition of perforin/granzyme B expression and nitric oxide release from MO/Mφ was normalized by NLGP. Altered status of signature cytokines, like, IL-12, IL-10, IL-6, TNFα from MO/Mφ under influence of Tregs is also rectified by NLGP. Tregs significantly enhanced the expression of altered marker, mannose receptor (CD206) on CD68(+) cells that was downregulated upon NLGP exposure. In addition to tumoricidal functions, antigen presenting ability of MO/Mφ is hampered by Treg induced downregulation of CD80, CD86 and HLA-ABC. NLGP upregulated these molecules in MO/Mφ even in the presence of Tregs. Treg mediated inhibition of MO/Mφ chemotaxis in contact dependent manner was also normalized partially by NLGP, where participation of CCR5 was documented. Overall results suggest that Treg influenced pro-tumor MO/Mφ functions are rectified in a significant extent by NLGP to create an anti-tumor immune environment.
Department of Immunoregulation Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
Tathagata
T
Chakraborty
Anamika
A
Bose
Kuntal Kanti
KK
Goswami
Shyamal
S
Goswami
Krishnendu
K
Chakraborty
Rathindranath
R
Baral
D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D031601:Azadirachta / Q000737:chemistry* / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D053804:Granzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D007624:KB Cells; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism; D054353:Perforin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D020298:U937 Cells
D006023:Glycoproteins; D007378:Interleukins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D010940:Plant Proteins; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D009569:Nitric Oxide; D053804:Granzymes