Cystic echinococcosis (CE) is a cosmopolitan zoonosis caused by the larval stage of the cestode parasite Echinococcus granulosus sensu lato (s.l.). Primary CE occurs in intermediate hosts (ungulates, accidentally humans) after ingestion of oncosphere-containing eggs, which develop into metacestodes (hydatid cysts) mainly in the host liver and lungs. Secondary CE occurs after spillage of protoscoleces from a fertile cyst within an infected intermediate host, since protoscoleces' developmental plasticity allows them to become new cysts within intermediate hosts or adult worms if ingested by definitive hosts (usually dogs). 1 Human studies on CE susceptibility/resistance are scarce, 2-4 although immune responses and host immunogenetics were suggested to determine the infection outcome. 5,6 Accordingly, studies performed in individuals seropositive for CE, but ultrasound normal, reported a unique antibody profile potentially associated with host resistance. 7 Additionally, mouse strains showing differences in susceptibility to secondary CE exhibited distinct parasite-specific immune responses. 8-10
Background: Invasive fungal diseases represent an unmet clinical need that could benefit from novel immunotherapeutic approaches. Host pattern-recognition receptors (e.g., Toll-like receptors, C-type lectins or Scavenger receptors) that sense conserved fungal cell wall constituents may provide suitable immunotherapeutic antifungal agents. Thus, we explored the therapeutic potential of the lymphocyte class I scavenger receptor CD5, a non-redundant component of the antifungal host immune response that binds to fungal β-glucans.
Methods: antifungal properties of the soluble ectodomain of human CD5 (shCD5) were assessed in vivo in experimental models of systemic fungal infection induced by pathogenic species (Candida albicans and Cryptococcus neoformans). In vitro mechanistic studies were performed by means of fungal-spleen cell co-cultures.
Results: shCD5-induced survival of lethally infected mice was dose and time-dependent and concomitant with reduced fungal load and increased leukocyte infiltration in primary target organ. Additive effects were observed in vivo after shCD5 was combined with sub-optimal doses of fluconazole. Ex vivo addition of shCD5 to fungal-spleen cell co-cultures increased release of pro-inflammatory cytokines involved in antifungal defence (TNF-α and IFN-γ) and reduced the number of viable C. albicans.
Conclusions: The results prompt further exploration of the adjunctive therapeutic potential of shCD5 in severe invasive fungal diseases.
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