title: Filaria-induced monocyte dysfunction and its reversal following treatment.
abstract: Monocyte dysfunction in filarial infection has been proposed as one mechanism underlying the diminished antigen-specific T-cell response seen in patent lymphatic filariasis. Cytokine/chemokine production and gene expression in monocytes from filaria-infected patients and uninfected healthy donors were assessed unstimulated and in response to stimulation with Staphylococcus aureus Cowan I bacteria plus gamma interferon both before and 8 months following treatment. Monocytes from filaria-infected individuals were studded with intracellular microfilarial antigens. Furthermore, monocytes from these individuals were less capable of producing interleukin-8 (IL-8), Exodus II, MIP-1alpha, MIP-1beta, and IL-1alpha and preferentially expressed genes involved in apoptosis and adhesion compared with monocytes from uninfected donors. Eight months following treatment with a single dose of ivermectin-albendazole, some of these defects were reversed, with monocyte production of IL-8, IL-1alpha, MIP-1alpha, and IL-10 being comparable to that seen in the uninfected controls. In addition, a marked increase in mRNA expression of genes associated with protein metabolism, particularly heat shock proteins, was seen compared with pretreatment expression. These data suggest that the function and gene expression of monocytes in filaria-infected patients are altered but that this dysfunction is partially reversible following antifilarial treatment.
authors.affiliation: Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, 4 Center Drive, Room 4/126, National Institutes of Health, Bethesda, Maryland 20892, USA. rsemnani@niaid.nih.gov
authors.forename: Roshanak Tolouei
authors.initials: RT
authors.lastname: Semnani
authors.forename: Paul B
authors.initials: PB
authors.lastname: Keiser
authors.forename: Yaya I
authors.initials: YI
authors.lastname: Coulibaly
authors.forename: Falaye
authors.initials: F
authors.lastname: Keita
authors.forename: Abdallah A
authors.initials: AA
authors.lastname: Diallo
authors.forename: Diakaridia
authors.initials: D
authors.lastname: Traore
authors.forename: Dapa A
authors.initials: DA
authors.lastname: Diallo
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Sekou F
authors.initials: SF
authors.lastname: Traore
authors.forename: Joseph
authors.initials: J
authors.lastname: Kubofcik
authors.forename: Amy D
authors.initials: AD
authors.lastname: Klion
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D015766:Albendazole / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use; D000977:Antiparasitic Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004605:Elephantiasis, Filarial / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology / Q000503:physiopathology; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007559:Ivermectin / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D016896:Treatment Outcome; D014958:Wuchereria bancrofti / Q000302:isolation & purification / Q000472:pathogenicity
chemical_list: D000871:Anthelmintics; D000977:Antiparasitic Agents; D006360:Heat-Shock Proteins; D007559:Ivermectin; D015766:Albendazole