title: Cellular therapy by allogeneic macrophages against visceral leishmaniasis: role of TNF-α.
abstract: Tumor necrosis factor α (TNF-α) is an essential player in infection with Leishmania, controlling inflammatory lesion and parasite killing. We recently have shown the leishmanicidal activity of transmembrane form of TNF (mTNF) derived from allogeneic natural killer (NK) cells in experimental visceral leishmaniasis. Allogeneic macrophages and human monocytes derived mTNF has significantly higher antileishmanial activity compared to allogeneic NK cells. Unlike NK cells, syngeneic macrophages also possess antileishmanial activity, although degree of activity is significantly less compared to allogeneic macrophages. Cellular therapy by intravenous transfer of allogeneic macrophages enhances leishmanicidal effect against the established infection in susceptible animal by reducing the splenic parasite burden to 28.3 ± 4.71 × 10(5) compared to 256.00 ± 17.36 × 10(5) in control group. In vivo treatment with anti-mouse TNF-α reduces the therapeutic efficacy of the allogeneic macrophages by increasing the parasite load in spleen of infected mice. These results demonstrated that allogeneic and xenogeneic macrophages induce cytokine mediated protective mechanism against infected macrophages via TNF-α in vitro and, possibly in vivo. The macrophage mediated protective role in absence of T cell help demonstrate an unique property of the mononuclear phagocytes in controlling infection and inflammation in visceral leishmaniasis, despite being acts as a host cell for the same parasite.
authors.affiliation: Immunobiology Laboratory, Banaras Hindu University, Varanasi 221005, India. Electronic address: pp_manna@yahoo.com.
authors.forename: Partha Pratim
authors.initials: PP
authors.lastname: Manna
authors.affiliation: Immunobiology Laboratory, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Sumit Kumar
authors.initials: SK
authors.lastname: Hira
authors.affiliation: National Brain Research Centre, Gurgaon, Haryana 122051, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
authors.affiliation: Indian Institute of Chemical Biology, Kolkata 700032, India.
authors.forename: Santu
authors.initials: S
authors.lastname: Bandyopadhyay
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D002460:Cell Line; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D007893:Leishmania donovani / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000628:therapy*; D008264:Macrophages / Q000276:immunology / Q000469:parasitology / Q000637:transplantation*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000637:transplantation; D013154:Spleen / Q000469:parasitology; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha
keywords: Adoptive cell therapy; Leishmania; Macrophage; TNF-α