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

Galectin-3 is a beta-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-gamma 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-1beta, 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-1beta serum levels detected in infected gal3(-/-) mice. Therefore galectin-3 may exert a regulatory role in innate immunity by diminishing IL-1beta production and thus affecting resistance to R. equi infection.

Oral administration of a live attenuated Salmonella vaccine strain expressing the VapA protein induces protection against infection by Rhodococcus equi.

Rhodococcus equi remains one of the most important pathogens of foals and vaccination strategies to prevent rhodococcosis are under increasing investigation. Attenuated Salmonella strains carrying heterologous antigens offer an advantageous alternative to conventional vaccines, especially because they induce mucosal and systemic immunity. In this work, we expressed the VapA antigen from R. equi in a Salmonella enterica Typhimurium strain, which was able to colonize and persist in the lymphoid tissue of BALB/c mice. Two days after being challenged, oral immunized mice presented a 3- to 7-fold increase in R. equi clearance. This was progressively enhanced during infection and, on the 10th day, a CFU value 50-fold lower than that recovered from non-immunized mice was attained. The number of hepatic granulomas was 2 times lower, and leukocyte infiltration was transiently detected in immunized mice, contrasting with the severe inflammation and necrosis presented by non-immunized mice. Infection with 1 x 10(7)R. equi CFU caused 100% mortality in the control groups, while all immunized mice survived. This protection was associated with the detection of high levels of anti-VapA IgG in the serum of the vaccinated mice, predominantly the IgG2a isotype. Our results suggest that attenuated Salmonella encoding VapA may be used in foals to prevent rhodococcosis.