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This Article Full Text (PDF) All Versions of this Article: jimmunol.0900257v1 183/2/916    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Metenou, S. Articles by Nutman, T. B. PubMed PubMed Citation Articles by Metenou, S. Articles by Nutman, T. B.

Patent Filarial Infection Modulates Malaria-Specific Type 1 Cytokine Responses in an IL-10-Dependent Manner in a Filaria/Malaria-Coinfected Population^1,2

Simon Metenou^*, Benoit Dembélé, Siaka Konate, Housseini Dolo, Siaka Y. Coulibaly, Yaya I. Coulibaly, Abdallah A. Diallo, Lamine Soumaoro, Michel E. Coulibaly, Dramane Sanogo, Salif S. Doumbia, Marissa Wagner, Sekou F. Traoré, Amy Klion^*, Siddhartha Mahanty^* and Thomas B. Nutman^*,3

*Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Filariasis Unit, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali

The effect of filarial infections on malaria-specific immune responses was investigated in Malian villages coendemic for filariasis (Fil) and malaria. Cytokines were measured from plasma and Ag-stimulated whole blood from individuals with Wuchereria bancrofti and/or Mansonella perstans infections (Fil⁺; n = 19) and those without evidence of filarial infection (Fil^–; n = 19). Plasma levels of IL-10 (geometric mean [GM], 22.8 vs 10.4) were higher in Fil⁺ compared with Fil^–, whereas levels of IFN-inducible protein (IP)-10 were lower in Fil⁺ (GM, 66.3 vs 110.0). Fil⁺ had higher levels of spontaneously secreted IL-10 (GM, 59.3 vs 6.8 pg/ml) and lower levels of IL-2 (1.0 vs 1.2 pg/ml) than did Fil^–. Although there were no differences in levels of Staphylococcus aureus enterotoxin B-induced cytokines between the two groups, Fil⁺ mounted lower IL-12p70 (GM, 1.11 vs 3.83 pg/ml; p = 0.007), IFN- (GM, 5.44 vs 23.41 pg/ml; p = 0.009), and IP-10 (GM, 29.43 vs 281.7 pg/ml; p = 0.007) responses following malaria Ag (MalAg) stimulation compared with Fil^–. In contrast, Fil⁺ individuals had a higher MalAg-specific IL-10 response (GM, 7318 pg/ml vs 3029 pg/ml; p = 0.006) compared with those without filarial infection. Neutralizing Ab to IL-10 (but not to TGFβ) reversed the down-regulated MalAg-specific IFN- and IP-10 (p < 0.001) responses in Fil⁺. Together, these data demonstrate that filarial infections modulate the Plasmodium falciparum-specific IL-12p70/IFN- secretion pathways known to play a key role in resistance to malaria and that they do so in an IL-10-dependent manner.

³ Address correspondence and reprint requests to Dr. Thomas B. Nutman, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, 4 Center Drive, Room B1-03, National Institutes of Health, Bethesda, MD 20892. E-mail address: tnutman{at}niaid.nih.gov

¹ This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

² Because S. Metenou, A. Klion, S. Mahanty, and T. B. Nutman are government employees and this is a government work, the work is in the public domain in the United States. Notwithstanding any other agreements, the National Institutes of Health reserves the right to provide the work to PubMed Central for display and use by the public, and PubMed Central may tag or modify the work consistent with its customary practices. You can establish rights outside of the United States subject to a government use license.

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