Role of the parasite-derived prostaglandin D2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection.
Epidermal Langerhans cells (LCs) play a key role in immune defense mechanisms and in numerous immunological disorders. In this report, we show that percutaneous infection of C57BL/6 mice with the helminth parasite Schistosoma mansoni leads to the activation of LCs but, surprisingly, to their retention in the epidermis. Moreover, using an experimental model of LC migration induced by tumor necrosis factor (TNF)-alpha, we show that parasites transiently impair the departure of LCs from the epidermis and their subsequent accumulation as dendritic cells in the draining lymph nodes. The inhibitory effect is mediated by soluble lipophilic factors released by the parasites and not by host-derived antiinflammatory cytokines, such as interleukin-10. We find that prostaglandin (PG)D2, but not the other major eicosanoids produced by the parasites, specifically impedes the TNF-alpha-triggered migration of LCs through the adenylate cyclase-coupled PGD2 receptor (DP receptor). Moreover, the potent DP receptor antagonist BW A868C restores LC migration in infected mice. Finally, in a model of contact allergen-induced LC migration, we show that activation of the DP receptor not only inhibits LC emigration but also dramatically reduces the contact hypersensitivity responses after challenge. Taken together, we propose that the inhibition of LC migration could represent an additional stratagem for the schistosomes to escape the host immune system and that PGD2 may play a key role in the control of cutaneous immune responses.
Angeli
V
V
Centre d'Immunologie et de Biologie Parasitaire, Institut National de la Santé et de la Recherche Médicale (INSERM) U547, Lille, France.
Faveeuw
C
C
Roye
O
O
Fontaine
J
J
Teissier
E
E
Capron
A
A
Wolowczuk
I
I
Capron
M
M
Trottein
F
F
D000818:Animals; D002465:Cell Movement; D000242:Cyclic AMP / Q000378:metabolism; D015777:Eicosanoids / Q000302:isolation & purification; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D016650:Fluorescein-5-isothiocyanate; D006827:Hydantoins / Q000494:pharmacology; D016753:Interleukin-10; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015230:Prostaglandin D2 / Q000276:immunology*; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000276:immunology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha
D015777:Eicosanoids; D006827:Hydantoins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C030669:BW 245C; D000242:Cyclic AMP; D016650:Fluorescein-5-isothiocyanate; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor