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

• Published in: The Journal of immunology (1950) Vol. 183; no. 2; pp. 916 - 924
• Main Authors: Metenou, Simon, Dembele, Benoit, Konate, Siaka, Dolo, Housseini, Coulibaly, Siaka Y, Coulibaly, Yaya I, Diallo, Abdallah A, Soumaoro, Lamine, Coulibaly, Michel E, Sanogo, Dramane, Doumbia, Salif S, Wagner, Marissa, Traore, Sekou F, Klion, Amy, Mahanty, Siddhartha, Nutman, Thomas B
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.07.2009
• Subjects: Animals; Cross Reactions - immunology; Cytokines - immunology; Cytokines - secretion; Endemic Diseases; Filariasis - complications; Filariasis - immunology; Humans; Immunity; Interferon-gamma - secretion; Interleukin-10 - blood; Interleukin-12 - secretion; Malaria, Falciparum - complications; Malaria, Falciparum - immunology; Plasmodium falciparum - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0900257

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-gamma (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 TGFbeta) reversed the down-regulated MalAg-specific IFN-gamma and IP-10 (p < 0.001) responses in Fil(+). Together, these data demonstrate that filarial infections modulate the Plasmodium falciparum-specific IL-12p70/IFN-gamma secretion pathways known to play a key role in resistance to malaria and that they do so in an IL-10-dependent manner.