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Infection and Immunity, August 2006, p. 4409-4417, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.01106-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Filaria-Induced Monocyte Dysfunction and Its Reversal following Treatment{dagger}

Roshanak Tolouei Semnani,1* Paul B. Keiser,1 Yaya I. Coulibaly,2 Falaye Keita,2 Abdallah A. Diallo,2 Diakaridia Traore,2 Dapa A. Diallo,2 Ogobara K. Doumbo,2 Sekou F. Traore,2 Joseph Kubofcik,1 Amy D. Klion,1 and Thomas B. Nutman1

Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,1 Departments of Epidemiology and Parasitic Diseases, University of Mali School of Medicine, Pharmacy, and Dentistry, Bamako, Mali2

Received 13 July 2005/ Returned for modification 30 August 2005/ Accepted 2 May 2006

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-1{alpha}, MIP-1ß, and IL-1{alpha} 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-1{alpha}, MIP-1{alpha}, 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.

* Corresponding author. Mailing address: LPD, NIAID, 4 Center Drive, Room 4/126, NIH, Bethesda, MD 20892. Phone: (301) 435-7873. Fax: (301) 480-3757. E-mail: rsemnani{at}niaid.nih.gov.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. F. Urban, Jr.

Infection and Immunity, August 2006, p. 4409-4417, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.01106-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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