Introduction
The larval stage of the cestode parasites in the Echinococcus
granulosus sensu lato species cluster cause cystic echinococcosis (CE)
in humans and livestock species (1, 2). The larva (hydatid) usually
grows within host organ’s parenchymae and is outwardly protected by the
massive acellular laminated layer (LL) (3–6). The LL is composed of a
mucin meshwork and deposits of the calcium salt of inositol
hexakisphosphate (InsP 6) (5, 7–10). Larval
growth is accompanied by shedding of LL particles, which in natural
infections are present in large amounts in the host tissues in the
parasite’s vicinity (11). In experimental intraperitoneal infections in
mice, the shed parasite materials are observed in the peritoneal cavity
(i.e. the infection site) and also in liver Kupffer cells, implying that
the materials circulate systemically (12). LL material uptake by Kupffer
cells is mostly dependent on the lectin receptor Clec4F, the only innate
immune receptor known to bind the LL mucin glycans (12, 13).
The local inflammatory reaction in CE is usually subdued, and vigorous
inflammation when present (especially with a granulomatous profile)
harms the parasite (14). The properties of the LL are thought to
contribute to local inflammatory control (2–4, 15–19). Indeed, LL
particles used as sole stimulus do not elicit inflammatory cytokines
from dendritic cells or macrophages, and they moderate the responses to
TLR agonists used as co-stimuli (16, 18). LL particles also inhibit
macrophage proliferation induced by exogenous IL-4 or M-CSF (19).
However, LL particles (freed of calcium InsP 6)
injected i.p. at a dose of 30 µg per mouse cause considerable
disappearance of resident peritoneal cavity macrophages together with
marginal recruitment of inflammatory macrophages (18), i.e. two
responses typical of inflammatory particulate stimuli (20–22).
Therefore, LL particles may have the potential to elicit inflammation,
especially at higher doses than those used in our previous study (18).
In this work, we have assessed cell recruitment after i.p. injection of
LL particles at a dose 5-fold higher than the highest dose used in our
previous work, and determined the contributions to the process of the
major components of the LL, namely calcium InsP 6and mucin glycans.