Patent filarial infection modulates malaria-specific type 1 cytokine responses in an IL-10-dependent manner in a filaria/malaria-coinfected population.

Abstract

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.

• Authors: 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, Thomas B Nutman
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 183 Issue 2 Pg. 916-24 (Jul 15 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19561105 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Cytokines
• Interleukin-10
• Interleukin-12
• Interferon-gamma

Topics

• Animals
• Cross Reactions (immunology)
• Cytokines (immunology, metabolism)
• Endemic Diseases
• Filariasis (complications, immunology)
• Humans
• Immunity
• Interferon-gamma (metabolism)
• Interleukin-10 (blood)
• Interleukin-12 (metabolism)
• Malaria, Falciparum (complications, immunology)
• Plasmodium falciparum (immunology)