Increased expression of CD25, CD83, and CD86, and secretion of IL-12, IL-23, and IL-10 by human dendritic cells incubated in the presence of Toll-like receptor 2 ligands and Giardia duodenalis.
BACKGROUND
Effects of Giardia duodenalis on dendritic cell (DC) functions may contribute to the pathogenesis of chronic giardiasis. G. duodenalis lysate has been shown to inhibit the activation of murine DCs through the ligands of various Toll-like receptors (TLRs), including TLR2 and TLR4. Our study aimed at translating these findings to human DCs.


RESULTS
As described previously for murine DCs, also human DCs were only weakly activated by the parasite itself. LPS-stimulated DCs incubated in the presence of G. duodenalis lysate produced less IL-12/23p40 (p = 0.002), IL-12p70 (p = 0.011), and IL-23 (p = 0.004), but more IL-10 (p = 0.006) than cells incubated in the absence of the parasite. Concomitantly, the expression of CD25, CD83, CD86, and HLA-DR was reduced on G. duodenalis-incubated DCs as compared to control cells. In contrast, human DCs stimulated through TLR2 in combination with TLR1 or TLR6 and G. duodenalis lysate secreted significantly more IL-12/23p40 (p = 0.006), IL-23 (p = 0.002), and IL-10 (p = 0.014) than cells stimulated through TLR2 ligands alone. Ligands for TLR2/TLR1 or TLR2/TLR6 also induced enhanced extracellular expression of CD25, CD83, and CD86 (p < 0.05).


CONCLUSIONS
In contrast to murine DCs, human DCs incubated in the presence of G. duodenalis and stimulated through TLR2 show increased activation as compared to cells incubated in the absence of the parasite. Thus, TLR2 ligands, e.g., delivered by probiotic lactobacilli, might be beneficial in human giardiasis through an adjuvant effect on the induction of cellular immune responses against G. duodenalis.
Janine
J
Obendorf
Pablo
P
Renner Viveros
Michael
M
Fehlings
Christian
C
Klotz
Toni
T
Aebischer
Institute of Tropical Medicine and International Health, Charité - Universitätsmedizin Berlin, Spandauer Damm 130, Berlin 14050, Germany. ralf.ignatius@charite.de.
Ralf
R
Ignatius
D015703:Antigens, CD / Q000032:analysis*; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000737:chemistry* / Q000276:immunology*; D016829:Giardia lamblia / Q000276:immunology*; D006801:Humans; D051194:Toll-Like Receptor 1 / Q000819:agonists; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D051216:Toll-Like Receptor 6 / Q000819:agonists
D015703:Antigens, CD; D016207:Cytokines; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6