Enhanced interleukin-12 and CD40 ligand activities but reduced Staphylococcus aureus Cowan 1-induced responses suggest a generalized and progressively impaired type 1 cytokine pattern for human schistosomiasis.
Whole-blood-cell cultures from schistosomiasis patients were stimulated with a variety of T-cell-dependent and T-cell-independent stimuli to determine whether the defect in type 1 cytokine expression observed following helminth infection is associated with alterations in interleukin-12 (IL-12) or CD40 ligand (CD40L) responsiveness. Cultures from uninfected individuals produced abundant gamma interferon in response to Staphylococcus aureus Cowan 1 (SAC), while patients with intestinal and hepatosplenic disease displayed intermediate and weak responses, respectively. Importantly, the decrease in type 1 cytokine expression was not attributed to defects in IL-12- or CD40L-induced activity. Indeed, schistosomiasis patients displayed heightened responses and even produced more biologically active IL-12 when stimulated with SAC and CD40L than did uninfected controls. Finally, additional studies suggested only a partial role for IL-10, since intestinal patients were the only group that overproduced this downregulatory cytokine. Together, these studies demonstrate that the type 1 deficiency in chronic hepatosplenic schistosomiasis is not related to specific defects in IL-12, IL-10, or CD40L activity, although changes in the functional status of antigen-presenting cells appear to be involved.
Montenegro
Silvia M L
SM
Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães-FIOCRUZ. Universidade Federal de Pernambuco, Recife, Brazil.
Abath
Frederico G C
FG
Domingues
Ana Lúcia C
AL
Melo
Wlademir G
WG
Morais
Clarice N L
CN
Coutinho
Eridan M
EM
Mahanty
Siddhartha
S
Wynn
Thomas A
TA
D000293:Adolescent; D000328:Adult; D000368:Aged; D023201:CD40 Ligand / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma