Antigen Presentation by CD1d Contributes to the Amplification of Th2 Responses to Schistosoma mansoni Glycoconjugates in Mice

Abstract

During murine schistosomiasis, there is a gradual switch from a predominant Th1 cytokine response to a Th2-dominated response after egg laying, an event that favors the formation of granuloma around viable eggs. Egg-derived glycoconjugates, including glycolipids, may play a crucial role in this phenomenon. In this study, we used a model of dendritic cell sensitization to study the role of egg glycoconjugates in the induction of specific immune response to soluble egg Ag (SEA) and to investigate the possibility that CD1d, a molecule implicated in glycolipid presentation, may be involved in such a phenomenon. We show that, when captured, processed, and presented to naive T lymphocytes by dendritic cells, egg, but not larval, Ag skew the immune response toward a Th2 response. Periodate treatment reversed this effect, indicating that the sugar moiety of SEA is important in this phenomenon. Using DC treated ex vivo with a neutralizing anti-CD1d Ab or isolated from CD1d knockout mice, we show that CD1d is crucial in the priming of SEA-specific Th2 lymphocytes. We then evaluated the contribution of CD1d on the development of the SEA-specific immune response and on the formation of the egg-induced liver granuloma during murine schistosomiasis. We find that CD1d knockout mice have a reduced Th2 response after egg laying and develop a less marked fibrotic pathology compared with wild-type mice. Altogether, our results suggest that Ag presentation of parasite glycoconjugates to CD1d-restricted T cells may be important in the early events leading to the induction of Th2 responses and to egg-induced pathology during murine schistosomiasis.

Role of CD1d in Coxsackievirus B3-Induced Myocarditis

“…MHC class I-like CD1 molecules are involved in innate immunity to many infectious agents (12)(13)(14)(15)(22)(23)(24)(25). Most often, CD1d-restricted cells belong to the invariant NKT subpopulation (12-15, 22, 24, 26), although T cells expressing noninvariant TCR have also been reported to be CD1 restricted (26 -28).…”

Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion

“…The preparation of SSA, SWAP and SEA was performed as described [42]. Young adult WT C57Bl/6 mice (6-8 weeks old) were purchased from Iffa Credo (l'Arbesle, France).…”

“…The worm burden was measured by liver perfusion 49 days after infection [42]. At the time of perfusion, the small intestines and the livers were also collected for the measurement of egg numbers within these organs.…”

Role of natural killer T lymphocytes during helminthic infection

“…We and others showed that glycoconjugates from egg Ags play crucial role in the Th2 response. This led us to hypothesize that egg glycolipids, through a CD1d-dependent mode of Ag presentation, could be important in this setting (Faveeuw et al, 2002;Okano et al, 1999). In agreement with this postulate, we found that CD1d-deficient ( -/-) BALB/c mice mounted a reduced Th2 response after the egg laying and developed a less marked fibrotic pathology, compared to wild type mice (Faveeuw et al, 2002).…”

“…This led us to hypothesize that egg glycolipids, through a CD1d-dependent mode of Ag presentation, could be important in this setting (Faveeuw et al, 2002;Okano et al, 1999). In agreement with this postulate, we found that CD1d-deficient ( -/-) BALB/c mice mounted a reduced Th2 response after the egg laying and developed a less marked fibrotic pathology, compared to wild type mice (Faveeuw et al, 2002). This observation was recently confirmed in S. mansoni-infected C57Bl/6 mice (Mallevaey et al, 2007), indicating that the genetic background does not appear to influence the regulatory impact of NKT functions on the global immune response in this model.…”