Patent filarial infection modulates malaria-specific type 1 cytokine responses in an IL-10-dependent manner in a filaria/malaria-coinfected population.
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.
Metenou
Simon
S
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Dembélé
Benoit
B
Konate
Siaka
S
Dolo
Housseini
H
Coulibaly
Siaka Y
SY
Coulibaly
Yaya I
YI
Diallo
Abdallah A
AA
Soumaoro
Lamine
L
Coulibaly
Michel E
ME
Sanogo
Dramane
D
Doumbia
Salif S
SS
Wagner
Marissa
M
Traoré
Sekou F
SF
Klion
Amy
A
Mahanty
Siddhartha
S
Nutman
Thomas B
TB
D000818:Animals; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D019353:Endemic Diseases; D005368:Filariasis / Q000150:complications* / Q000276:immunology; D006801:Humans; D007109:Immunity; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood*; D018664:Interleukin-12 / Q000378:metabolism; D016778:Malaria, Falciparum / Q000150:complications* / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology
D016207:Cytokines; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma