In attempts to investigate the role of galectin-3 in innate immunity, we studied galectin-3-deficient (gal3 ؊/؊ ) mice with regard to their response to Toxoplasma gondii infection, which is characterized by inflammation in affected organs, Th-1-polarized immune response, and accumulation of cysts in the central nervous system. In wild-type (gal3 ؉/؉ ) mice, infected orally, galectin-3 was highly expressed in the leukocytes infiltrating the intestines, liver, lungs, and brain. Compared with gal3 ؉/؉ , infected gal3 ؊/؊ mice developed reduced inflammatory response in all of these organs but the lungs. Brain of gal3 ؊/؊ mice displayed a significantly reduced number of infiltrating monocytes/macrophages and CD8 ؉ cells and a higher parasite burden. Furthermore, gal3 ؊/؊ mice mounted a higher Th1-polarized response and had comparable survival rates on peroral T. gondii infection, even though they were more susceptible to intraperitoneal infection. Interestingly, splenic cells and purified CD11c ؉ dendritic cells from gal3 ؊/؊ mice produced higher amounts of interleukin-12 than cells from gal3 ؉/؉ mice, possibly explaining the higher Th1 response verified in the gal3 ؊/؊ mice. We conclude that galectin-3 exerts an important role in innate immunity, including not only a proinflammatory effect but also a regulatory role on dendritic cells, capable of interfering in the adaptive immune response.

Galectin-3 (Gal 3) is a glycan-binding protein that can be secreted by activated macrophages and mast cells at inflammation sites and plays an important role in inflammatory diseases caused by Bacteria and their products, such as lipopolysaccharides (LPS). Although it is well established that Gal 3 can interact with LPS, the pathophysiological importance of LPS/Gal 3 interactions is not fully understood. Data presented herein demonstrate for the first time that the interaction of Gal 3, either via its carbohydrate binding C-terminal domain or via its N-terminal part, with LPS from different bacterial strains, enhances the LPS-mediated neutrophil activation in vitro. Gal 3 allowed low LPS concentrations (1 µg/mL without serum, 1 ng/mL with serum) to upregulate CD11b expression and reactive oxygen species (ROS) generation on human neutrophils in vitro and drastically enhanced the binding efficiency of LPS to the neutrophil surface. These effects required LPS preincubation with Gal 3, before neutrophil stimulation and involved specific Gal 3/LPS interaction. A C-terminal Gal-3 fragment, which retains the lectin domain but lacks the N-terminal part, was still able to bind both to Escherichia coli LPS and to neutrophils, but had lost the ability to enhance neutrophil response to LPS. This result emphasizes the importance of an N-terminus-mediated Gal 3 oligomerization induced by its interaction with LPS. Finally we demonstrated that Balb/C mice were more susceptible to LPS-mediated shock when LPS was pretreated with Gal 3. Altogether, these results suggest that multimeric interactions between Gal 3 oligomers and LPS potentiate its pro-inflammatory effects on neutrophils.

No abstract

No abstract

The piRNA pathway is a surveillance system that guarantees oogenesis and adult fertility in a range of animal species. The pathway is centered on PIWI clade Argonaute proteins and the associated small non-coding RNAs termed piRNAs. In this study, we set to investigate the evolutionary conservation of the piRNA pathway in the hemimetabolous insect Rhodnius prolixus. Our transcriptome profiling reveals that core components of the pathway are expressed during previtellogenic stages of oogenesis. Rhodnius’ genome harbors four putative piwi orthologs. We show that Rp-piwi2, Rp-piwi3 and Rp-ago3, but not Rp-piwi1 transcripts are produced in the germline tissues and maternally deposited in the mature eggs. Consistent with a role in Rhodnius oogenesis, parental RNAi against the Rp-piwi2, Rp-piwi3 and Rp-ago3 results in severe egg laying and female adult fertility defects. Furthermore, we show that the reduction of the Rp-piwi2 levels by parental RNAi disrupts oogenesis by causing a dramatic loss of trophocytes, egg chamber degeneration and oogenesis arrest. Intriguingly, the putative Rp-Piwi2 protein features a polyglutamine tract at its N-terminal region, which is conserved in PIWI proteins encoded in the genome of other Triatomine species. Together with R. prolixus, these hematophagous insects are primary vectors of the Chagas disease. Thus, our data shed more light on the evolution of the piRNA pathway and provide a framework for the development of new control strategies for Chagas disease insect vectors.