Filaria/Wolbachia activation of dendritic cells and development of Th1-associated responses is dependent on Toll-like receptor 2 in a mouse model of ocular onchocerciasis (river blindness).
Toll-like receptors (TLRs) regulate dendritic cell function and activate signals that mediate the nature of the adaptive immune response. The current study examined the role of TLRs in dendritic cell activation and in regulating T cell and antibody responses to antigens from the filarial parasites Onchocerca volvulus and Brugia malayi, which cause river blindness and lymphatic filariasis, respectively. Bone-marrow-derived CD11c(+) cells from C57BL/6 and TLR4(-/-) mice produced high levels of IL-6 and RANTES, and showed elevated surface CD40 expression, whereas CD11c(+) cells from myeloid differentiation factor 88(-/-) (MyD88(-/-)), TLR2(-/-) and TLR2/4(-/-) mice were not activated. Similarly, IFN-gamma production by splenocytes from immunized TLR2(-/-) mice was significantly impaired compared with splenocytes from C57BL/6 and TLR4(-/-) mice. In contrast, there was no difference among these strains in Th2-associated responses including IL-5 production by splenocytes from immunized animals, serum IgE and IgG(1), or eosinophil infiltration into the corneal stroma. Neutrophil recruitment to the cornea and CXC chemokine production was inhibited in immunized TLR2(-/-) mice compared with C57BL/6 and TLR4(-/-) mice. Taken together, these findings demonstrate an essential role for TLR2 in filaria-induced dendritic cell activation, IFN-gamma production and neutrophil migration to the cornea, but does not affect filaria-induced Th2-associated responses.
Daehnel
K
K
Department of Ophthalmology, Case Western Reserve University, Cleveland, OH 44106-7286, USA.
Gillette-Ferguson
I
I
Hise
A G
AG
Diaconu
E
E
Harling
M J
MJ
Heinzel
F P
FP
Pearlman
E
E
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D017178:Brugia malayi / Q000276:immunology; D003315:Cornea / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017181:Onchocerca volvulus / Q000276:immunology*; D015827:Onchocerciasis, Ocular / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism
D000909:Antibodies, Helminth; D015703:Antigens, CD; D016207:Cytokines; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4