Galectin-3 is a b-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 À/À ) and their wild-type counterpart (gal3 1/1 ) revealed that the LD 50 for the gal3 À/À mice was about seven times higher than that for the gal3 1/1 mice. When challenged with a sublethal dose, gal3 À/À mice showed lower bacteria counts and higher production of IL-12 and IFN-c production, besides exhibiting a delayed although increased inflammatory reaction. Gal3 À/À macrophages exhibited a decreased frequency of bacterial replication and survival, and higher transcript levels of IL-1b, IL-6, IL-10, TLR2 and MyD88. R. equi-infected gal3 1/1 macrophages showed decreased expression of TLR2, whereas R. equi-infected gal3 À/À macrophages showed enhanced expression of this receptor. Furthermore, galectin-3 deficiency in macrophages may be responsible for the higher IL-1b serum levels detected in infected gal3 À/À mice. Therefore galectin-3 may exert a regulatory role in innate immunity by diminishing IL-1b production and thus affecting resistance to R. equi infection.Key words: Bacterial infections . Galectin-3 . IL-1b . Innate immunity . Toll-like receptor IntroductionActivation of resident macrophages is one of the earliest events in the cellular host response to microbial invasion, and macrophage-derived cytokines play a key role in the initiation and amplification of the inflammatory process as well as in the regulation of the immune response. On the basis of its capacity to recognize carbohydrates and its abundant expression in activated macrophages [1,2], galectin-3 has been considered an important factor in the interaction of host cells with microorganisms [3]. Extracellular galectin-3 is able to activate cells [4][5][6][7][8][9] cell-cell and cell-extracellular matrix interactions [10][11][12], and induce phagocyte migration [13]. However, galectin-3 also functions inside the cells and can contribute to macrophage functions that are essential in the cellular response during the infectious process, such as cell survival [14] and phagocytosis [15].As a result of its ability to recognize glycans containing b-galactoside, galectin-3 binds to glycoconjugates synthesized by several pathogens such as Mycobacterium tuberculosis [16], Leishmania major [17], Trypanosoma cruzi [18], Schistosoma mansoni [19] and Candida albicans [20]. Recently, galectin-3 and TLR2 have been found to be associated in C. albicans-infected differentiated macrophages, an association that has been considered essential for TLR2-dependent cytokine production in response to the fungal infection [21]. Therefore, galectin-3 has been considered as a novel pattern recognition receptor, acting either alone or in ...

Conventional vaccines to prevent the pneumonia caused by Rhodococcus equi have not been successful. We have recently demonstrated that immunization with Salmonella enterica Typhimurium expressing the VapA antigen protects mice against R. equi infection. We now report that oral vaccination of mice with this recombinant strain results in high and persistent fecal levels of antigen-specific IgA, and specific proliferation of the spleen cells of immunized mice in response to the in vitro stimulation with R. equi antigen. After in vitro stimulation, spleen cells of immunized mice produce high levels of Th1 cytokines and show a prominent mRNA expression of the Th1 transcription factor T-bet, in detriment of the Th2 transcription factor GATA-3. Following R. equi challenge, a high H2O2, NO, IL-12, and IFN-γ content is detected in the organs of immunized mice. On the other hand, TNF-α and IL-4 levels are markedly lower in the organs of vaccinated mice, compared with the non-vaccinated ones. The IL-10 content and the mRNA transcription level of TGF-β are also higher in the organs of immunized mice. A greater incidence of CD4+ and CD8+ T cells and B lymphocytes is verified in vaccinated mice. However, there is no difference between vaccinated and non-vaccinated mice in terms of the frequency of CD4+CD25+Foxp3+ T cells. Finally, we show that the vaccination confers a long-term protection against R. equi infection. Altogether, these data indicate that the oral vaccination of mice with S. enterica Typhimurium expressing VapA induces specific and long-lasting humoral and cellular responses against the pathogen, which are appropriately regulated and allow tissue integrity after challenge.

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