Resistance of the Echinococcus granulosus cyst wall to complement activation: analysis of the role of InsP6 deposits

Irigoı́n, Florencia; Laich, Andreas; Ferreira, Ana Maria da Costa; Fernández, Cecilia; Sim, Robert B.; Díaz, Álvaro

doi:10.1111/j.1365-3024.2008.01034.x

Cited by 15 publications

(14 citation statements)

References 34 publications

(62 reference statements)

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“…The issue has been addressed for the complement system, where triggering of this cascade by the LL is much less effective than that by other E. granulosus materials (3, 20, 21). For innate immune cells, two studies focusing on nitric oxide production by macrophages showed that LL-derived materials inhibit this response in cells stimulated with lipopolysaccharide (LPS) or gamma interferon (IFN-γ) (22, 23).…”

Section: Introductionmentioning

confidence: 99%

Unconventional Maturation of Dendritic Cells Induced by Particles from the Laminated Layer of Larval Echinococcus granulosus

et al. 2014

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The larval stage of the cestode parasite Echinococcus granulosus causes hydatid disease in humans and livestock. This infection is characterized by the growth in internal organ parenchymae of fluid-filled structures (hydatids) that elicit surprisingly little inflammation in spite of their massive size and persistence. Hydatids are protected by a millimeter-thick layer of mucin-based extracellular matrix, termed the laminated layer (LL), which is thought to be a major factor determining the host response to the infection. Host cells can interact both with the LL surface and with materials that are shed from it to allow parasite growth. In this work, we analyzed the response of dendritic cells (DCs) to microscopic pieces of the native mucin-based gel of the LL (pLL). In vitro, this material induced an unusual activation state characterized by upregulation of CD86 without concomitant upregulation of CD40 or secretion of cytokines (interleukin 12 [IL-12], IL-10, tumor necrosis factor alpha [TNF-α], and IL-6). When added to Toll-like receptor (TLR) agonists, pLL-potentiated CD86 upregulation and IL-10 secretion while inhibiting CD40 upregulation and IL-12 secretion. In vivo, pLL also caused upregulation of CD86 and inhibited CD40 upregulation in DCs. Contrary to expectations, oxidation of the mucin glycans in pLL with periodate did not abrogate the effects on cells. Reduction of disulfide bonds, which are known to be important for LL structure, strongly diminished the impact of pLL on DCs without altering the particulate nature of the material. In summary, DCs respond to the LL mucin meshwork with a “semimature” activation phenotype, both in vitro and in vivo.

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Section: Introductionmentioning

confidence: 99%

Unconventional Maturation of Dendritic Cells Induced by Particles from the Laminated Layer of Larval Echinococcus granulosus

et al. 2014

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“…We have not observed differences between preparations containing or lacking this component with respect to DC/macrophage responses . The deposits give rise to an enormous surface for protein adsorption, and host proteins that associate with the LL (except for specific antibodies) tend to be adsorbed on this component . These deposits might therefore act as the ‘sticky pad’ for conventional protein antigens, leading to their targeting to liver macrophages, and/or their uptake by DCs that are concomitantly conditioned by LL particles .…”

Section: Molecules Making Up the Llmentioning

confidence: 82%

“…The so‐called alternative pathway of complement activation is controlled on the LL through binding the soluble host regulator factor H . Factor H‐dependent inactivation of the covalently deposited active form of the central component C3 is unaffected by previous extraction of calcium Ins P 6 . This suggests that there are functional sites for factor H on the LL mucins, but the nature of such sites is still unknown.…”

Section: Molecules Making Up the Llmentioning

confidence: 99%

“…This suggests that there are functional sites for factor H on the LL mucins, but the nature of such sites is still unknown. The Ins P 6 deposits selectively bind C1q, the recognition molecule of the first component of the classical pathway . Such direct binding of C1q to surfaces bearing repetitive negative charges can in other contexts initiate classical pathway activation .…”

Section: Molecules Making Up the Llmentioning

confidence: 99%

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Parasite molecules and host responses in cystic echinococcosis

Díaz

Casaravilla

Barrios

et al. 2016

Parasite Immunology

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Cystic echinococcosis is the infection by the larvae of cestode parasites belonging to the Echinococcus granulosus sensu lato species complex. Local host responses are strikingly subdued in relation to the size and persistence of these larvae, which develop within mammalian organs as 'hydatid cysts' measuring up to tens of cm in diameter. In a context in which helminth-derived immune-suppressive, as well as Th2-inducing, molecules garner much interest, knowledge on the interactions between E. granulosus molecules and the immune system lags behind. Here, we discuss what is known and what are the open questions on E. granulosus molecules and structures interacting with the innate and adaptive immune systems, potentially or in demonstrated form. We attempt a global biological approach on molecules that have been given consideration primarily as protective (Eg95) or diagnostic antigens (antigen B, antigen 5). We integrate glycobiological information, which traverses the discussions on antigen 5, the mucin-based protective laminated layer and immunologically active preparations from protoscoleces. We also highlight some less well-known molecules that appear as promising candidates to possess immune-regulatory activities. Finally, we point out gaps in the molecular-level knowledge of this infectious agent that hinder our understanding of its immunology.

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“…Echinococcus granulosus , a cestode that causes cystic echinococcosis in humans, expresses a protein that sequestrates FH on the hydatid cyst wall to inhibit complement C3b deposition (Diaz et al, 1997; Breijo et al, 2008). The binding molecule remained unknown until further research showed that it was InsP6, a major component of the acellular laminated layer (LL) of the hydatid cyst wall, that was bound with FH to inhibit the alternative pathway (Irigoin et al, 2008). Mosquito midgut epithelial cells also express two proteins (40 and 100 kDa) as receptors that captured FH to inhibit the deposition of C3b and impair activation of the alternative complement pathway (Khattab et al, 2015).…”

Section: Complement Evasion By Parasitesmentioning

confidence: 99%

Complement Evasion: An Effective Strategy That Parasites Utilize to Survive in the Host

et al. 2019

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Parasitic infections induce host immune responses that eliminate the invading parasites. However, parasites have evolved to develop many strategies to evade host immune attacks and survive in a hostile environment. The complement system acts as the first line of immune defense to eliminate the invading parasites by forming the membrane attack complex (MAC) and promoting an inflammatory reaction on the surface of invading parasites. To date, the complement activation pathway has been precisely delineated; however, the manner in which parasites escape complement attack, as a survival strategy in the host, is not well understood. Increasing evidence has shown that parasites develop sophisticated strategies to escape complement-mediated killing, including (i) recruitment of host complement regulatory proteins on the surface of the parasites to inhibit complement activation; (ii) expression of orthologs of host RCA to inhibit complement activation; and (iii) expression of parasite-encoded proteins, specifically targeting different complement components, to inhibit complement function and formation of the MAC. In this review, we compiled information regarding parasitic abilities to escape host complement attack as a survival strategy in the hostile environment of the host and the mechanisms underlying complement evasion. Effective escape of host complement attack is a crucial step for the survival of parasites within the host. Therefore, those proteins expressed by parasites and involved in the regulation of the complement system have become important targets for the development of drugs and vaccines against parasitic infections.

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Resistance of the Echinococcus granulosus cyst wall to complement activation: analysis of the role of InsP₆ deposits

Cited by 15 publications

References 34 publications

Unconventional Maturation of Dendritic Cells Induced by Particles from the Laminated Layer of Larval Echinococcus granulosus

Unconventional Maturation of Dendritic Cells Induced by Particles from the Laminated Layer of Larval Echinococcus granulosus

Parasite molecules and host responses in cystic echinococcosis

Complement Evasion: An Effective Strategy That Parasites Utilize to Survive in the Host

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