Lack of galectin-3 alters the balance of innate immune cytokines and confers resistance to Rhodococcus equi infection

Galectin-3 is a β-galactoside-binding lectin implicated in the fine-tuning of innate immunity. Rhodococcus equi, a facultative intracellular bacterium of macrophages, causes severe granulomatous bronchopneumonia in young horses and immunocompromised humans. The aim of this study is to investigate the role of galectin-3 in the innate resistance mechanism against R. equi infection. The bacterial challenge of galectin-3-deficient mice (gal3^-/-) and their wild-type counterpart (gal3^+/+) revealed that the LD₅₀ for the gal3^-/- mice was about seven times higher than that for the gal3^+/+ mice. When challenged with a sublethal dose, gal3^-/- mice showed lower bacteria counts and higher production of IL-12 and IFN-γ production, besides exhibiting a delayed although increased inflammatory reaction. Gal3^-/- macrophages exhibited a decreased frequency of bacterial replication and survival, and higher transcript levels of IL-1β, IL-6, IL-10, TLR2 and MyD88. R. equi-infected gal3^+/+ macrophages showed decreased expression of TLR2, whereas R. equi-infected gal3^-/- macrophages showed enhanced expression of this receptor. Furthermore, galectin-3 deficiency in macrophages may be responsible for the higher IL-1β serum levels detected in infected gal3^-/- mice. Therefore galectin-3 may exert a regulatory role in innate immunity by diminishing IL-1β production and thus affecting resistance to R. equi infection.