Inefficient and abortive classical complement pathway activation by the calcium inositol hexakisphosphate component of the Echinococcus granulosus laminated layer

Anabella A. Barrios, Leticia Grezzi, Sebastián Miles, Mara Mariconti, Gustavo Mourglia-Ettlin, Paula I. Seoane, Alvaro Díaz

Research output: Contribution to journalArticle

Abstract

Persistent extracellular tissue-dwelling pathogens face the challenge of antibody-dependent activation of the classical complement pathway (CCP). A prime example of this situation is the larva of the cestode Echinococcus granulosus sensu lato, causing cystic echinococcosis. This tissue-dwelling, bladder-like larva is bounded by a cellular layer protected by the outermost acellular “laminated layer” (LL), to which host antibodies bind. The LL is made up of a mucin meshwork and interspersed nano-deposits of calcium inositol hexakisphosphate (calcium InsP6). We previously reported that calcium InsP6 bound C1q, apparently initiating CCP activation. The present work dissects CCP activation on the LL. Most of the C1 binding activity in the LL corresponded to calcium InsP6, and this binding was enhanced by partial proteolysis of the mucin meshwork. The remaining C1 binding activity was attributable to host antibodies, which included CCP-activating IgG isotypes. Calcium InsP6 made only a weak contribution to early CCP activation on the LL, suggesting inefficient C1 complex activation as reported for other polyanions. CCP activation on calcium InsP6 gave rise to a dominant population of C3b deposited onto calcium InsP6 itself that appeared to be quickly inactivated. Apparently as a result of inefficient initiation plus C3b inactivation, calcium InsP6 made no net contribution to C5 activation. We propose that the LL protects the underlying parasite cells from CCP activation through the combined effects of inefficient permeation of C1 through the mucins and C1 retention on calcium InsP6. This mechanism does not result in C5 activation, which is known to drive parasite-damaging inflammation.

Original languageEnglish
JournalImmunobiology
DOIs
Publication statusPublished - Jan 1 2019

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Keywords

  • C1q
  • Classical complement pathway
  • Cystic echinococcosis
  • Factor H
  • Helminth
  • Hydatid disease
  • Inositol hexakisphosphate

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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