title: Filarial antigens mediate apoptosis of human monocytes through Toll-like receptor 4.
abstract: BACKGROUND
  Apoptosis of several host cells induced by parasites/parasite products has been investigated in human filariasis to understand immune hyporesponsiveness. However, apoptosis of monocytes-one of the major antigen presenting cells in peripheral circulation, which are chronically exposed to filarial antigens in infected subjects-is yet to be understood.
  
  
  METHODS
  Apoptosis of human monocytes with Brugia pahangi antigen (BpA) was demonstrated by scoring several apoptotic markers using flow cytometry. Ability of BpA and plasma of infected subjects to suppress lymphocyte proliferation was demonstrated by (3)H thymidine incorporation assay and carboxyfluorescein succinimidyl ester dilution assay.
  
  
  RESULTS
  BpA induced significant apoptosis of normal human monocytes, primarily through Toll-like receptor 4 (TLR4), and suppressed phytohemagglutinin (PHA)-mediated proliferation of normal human T lymphocytes. However, monocytes of Wuchereria bancrofti-infected subjects were resistant to BpA-induced apoptosis. Plasma of infected subjects also mediated apoptosis of normal monocytes, presumably due to circulating filarial antigens, and resulted in inhibition of PHA-induced proliferation.
  
  
  CONCLUSIONS
  Normal human monocytes were found to be qualitatively different from those of filariasis-infected subjects; whereas filarial antigens mediate apoptosis of normal human monocytes through TLR4, those of infected subjects were found to be resistant.
authors.affiliation: Infectious Disease Biology Group.
authors.forename: Alok
authors.initials: A
authors.lastname: Das Mohapatra
authors.affiliation: Infectious Disease Biology Group.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Panda
authors.affiliation: Department of Gene Function and Regulation, Institute of Life Sciences.
authors.forename: Anjan Kumar
authors.initials: AK
authors.lastname: Pradhan
authors.affiliation: Infectious Disease Biology Group.
authors.forename: Birendra Kumar
authors.initials: BK
authors.lastname: Prusty
authors.affiliation: Department of Immunology, Regional Medical Research Center, Indian Council of Medical Research, Bhubaneswar, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Satapathy
authors.affiliation: Infectious Disease Biology Group.
authors.forename: Balachandran
authors.initials: B
authors.lastname: Ravindran
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis; D017179:Brugia pahangi / Q000276:immunology*; D049109:Cell Proliferation; D015331:Cohort Studies; D005368:Filariasis / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance; D009000:Monocytes / Q000276:immunology* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D014958:Wuchereria bancrofti / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: TLR4; apoptosis; filariasis; immunosuppression; monocytes