The lymphocytic scavenger receptor CD5 shows therapeutic potential in mouse models of fungal infection.

Abstract

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. albicansConclusions: The results prompt further exploration of the adjunctive therapeutic potential of shCD5 in severe invasive fungal diseases.