Echinococcus granulosus glycoconjugates induce peritoneal B cell differentiation into antibody‐secreting cells and cytokine production

Abstract

Helminth parasite infections are associated with predominant Th2-type cytokine responses, and parasite glycoconjugates have been recognized as partially responsible for such immune bias. It has been proved that Echinococcus granulosus evokes a Th2-type cytokine pattern characterized by a high production of IL-4, IL-5, IL-6 and IL-10, and no or mild IFN-γ levels in animal models and in patients with cystic echinococcosis, respectively. Here, we show that E4(+) (a glycoconjugate-enriched fraction from E. granulosus protoscolex) stimulated the secretion of a high concentration of IL-6, followed by IL-10 and TNF-α by normal peritoneal B cells. We determined that E4(+) bound to the surface of peritoneal B cells and induced their activation and, also, triggered the differentiation of peritoneal B cells into IgM-, IgG2b- and IgG3-secreting cells in a T-independent way. Interestingly, the IgM released by E4(+) -stimulated peritoneal B cells from normal mice recognized protoscolex antigens. Results showed that, after the encounter with antigens from E. granulosus protoscolex, peritoneal B cells are a source of Th2-type cytokines and polyclonal antibodies, some of which recognize parasite antigens, suggesting that peritoneal B cells can condition the outcome of the infection.

The excretory-secretory products of Echinococcus granulosus protoscoleces directly regulate the differentiation of B10, B17 and Th17 cells

“…A previous study found that a glycoconugate-enriched fraction from EgPSC stimulated the secretion of IL-10 production by peritoneal B cells [25]. However, whether this process is directly triggered by ESPs remains to be established.…”

The intermediate host immune response in cystic echinococcosis

“…PSC carbohydrate fractions are immunodominant in both mice and humans and are mainly recognized by IgG4 in humans, an isotype with poor ability to induce complement and cell activation . PSC carbohydrate fractions (E4 + ) have also been shown to induce IL‐10 and to reduce splenocyte proliferation in vitro . Moreover, PSC present Fc‐binding activity, which could interfere with effector functions of human IgG1 and IgG3 (Figure b).…”

Echinococcosis

“…Increased Th1 responses (IFNγ or IL-12) impair PSC survival and cyst development, while IL-4 and IL-10 induce heavier cyst loads and impair PSC killing (Al-Qaoud and Abdel-Hafez 2008; Amri et al 2007Amri et al , 2009). Other mechanisms of immune evasion include polyclonal activation of B cells (Cox et al 1989) and induction of IL-10, IgG4, and high levels of nonspecific antibodies and lack of antibody avidity maturation, as shown experimentally by injection of carbohydrate fractions of PSC (Miguez et al 1996;Mourglia-Ettlin et al 2011a;Ferragut and Nieto 1996;Severi et al 1997;Baz et al 1999Baz et al , 2008Cardozo et al 2002;Dematteis et al 2001). Moreover, PSC present Fc-binding activity (Baz et al 1998) and express immune regulatory antigen B and EgTeg (Ortona et al 2005;Sanchez et al 1991;Monteiro et al 2010).…”