Galectins are a group of evolutionarily conserved proteins with the ability to bindβ-galactosides through characteristic carbohydrate-recognition domains (CRD). Galectin-3 is structurally unique among all galectins as it contains a C-terminal CRD linked to an N-terminal protein-binding domain, being the only chimeric galectin. Galectin-3 participates in many functions, both intra- and extracellularly. Among them, a prominent role for Galectin-3 in inflammation has been recognized. Galectin-3 has also been shown to directly bind to pathogens and to have various effects on the functions of the cells of the innate immune system. Thanks to these two properties, Galectin-3 participates in several ways in the innate immune response against invading pathogens. Galectin-3 has been proposed to function not only as a pattern-recognition receptor (PRR) but also as a danger-associated molecular pattern (DAMP). In this review, we analyze the various roles that have been assigned to Galectin-3, both as a PRR and as a DAMP, in the context of immune responses against pathogenic microorganisms.

During inflammation, cell surface adhesion molecules guide the adhesion and migration of circulating leukocytes across the endothelial cells lining the blood vessels to access the site of injury. The transmembrane molecule CD13 is expressed on monocytes and endothelial cells and has been shown to mediate homotypic cell adhesion, which may imply a role for CD13 in inflammatory monocyte trafficking. Here, we show that ligation and clustering of CD13 by mAb or viral ligands potently induce myeloid cell/endothelial adhesion in a signal transduction-dependent manner involving monocytic cytoskeletal rearrangement and filopodia formation. Treatment with soluble recombinant (r)CD13 blocks this CD13-dependent adhesion, and CD13 molecules from monocytic and endothelial cells are present in the same immunocomplex, suggesting a direct participation of CD13 in the adhesive interaction. This concept is strengthened by the fact that activated monocytic cells adhere to immobilized recombinant CD13. Furthermore, treatment with anti-CD13 antibodies in a murine model of peritonitis results in a decrease in leukocyte infiltration into the peritoneum, suggesting a potential role for CD13 in leukocyte trafficking in vivo. Therefore, this work supports a new direction for CD13 biology, where these cell surface molecules act as true molecular interfaces that induce and participate in critical inflammatory cell interactions.

The transforming growth factor-β(TGF-β) superfamily is a family of structurally related proteins that includes TGF-β, activins/inhibins, and bone morphogenic proteins (BMPs). Members of the TGF-βsuperfamily regulate cellular functions such as proliferation, apoptosis, differentiation, and migration and thus play key roles in organismal development. TGF-βis involved in several human diseases, including autoimmune disorders and vascular diseases. Activation of the TGF-βreceptor induces phosphorylation of serine/threonine residues and triggers phosphorylation of intracellular effectors (Smads). Once activated, Smad proteins translocate to the nucleus and induce transcription of their target genes, regulating various processes and cellular functions. Recently, there has been an attempt to correlate the effect of TGF-βwith various pathological entities such as allergic diseases and cancer, yielding a new area of research known as “allergooncology," which investigates the mechanisms by which allergic diseases may influence the progression of certain cancers. This knowledge could generate new therapeutic strategies aimed at correcting the pathologies in which TGF-βis involved. Here, we review recent studies that suggest an important role for TGF-βin both allergic disease and cancer progression.

In response to microenvironmental cues, macrophages undergo a profound phenotypic transformation acquiring distinct activation phenotypes ranging from proinflammatory (M1) to anti-inflammatory (M2). To study how activation phenotype influences phagocytosis and production of reactive oxygen species (ROS) mediated by receptors for IgG antibodies (Fc receptors) and by CD13, human monocyte-derived macrophages were polarized to distinct phenotypes using IFN-gamma(Mph-IFNγ), IL-4 (Mph-IL-4), or IL-10 (Mph-IL-10). Phenotypically, Mph-IFNγ were characterized as CD14+CD80+CD86+ cells, Mph-IL-4 as CD209highCD206+CD11b+CD14low, and Mph-IL10 as CD16+CD163+ cells. As compared to non-polarized macrophages, FcgRI expression increased in Mph-IFNγ and Mph-IL10, and FcgRIII expression increased in Mph-IL-10. None of the polarizing cytokines modified FcgRII or CD13 expression. Functionally, we found that cytokine-mediated activation significantly and distinctively affected FcgR- and CD13-mediated phagocytosis and ROS generation. As compared to non-polarized macrophages, FcgRI-, FcgRII- and CD13-mediated phagocytosis was significantly increased in Mph-IL-10, and decreased in Mph-IFNγ, although both cytokines significantly upregulated FcgRI expression. IL-10 also increased phagocytosis of E. coli, showing that the effect of IL-10 on macrophage phagocytosis is not specific for a particular receptor. Interestingly, Mph-IL-4, which showed poor FcγR- and CD13-mediated phagocytosis, showed very high phagocytosis of E. coli and zymosan. Coupled with phagocytosis, macrophages produce ROS that contribute to microbial killing. As expected, Mph-IFNγ showed significant production of ROS after FcgRI-, FcgRII- or CD13-mediated phagocytosis. Unexpectedly, we found that Mph-IL-10 can also produce ROS after simultaneous stimulation through several phagocytic receptors, as coaggregation of FcgRI/FcgRII/CD13 induced a belated but significant ROS production. Together, these results demonstrate that activation of macrophages by each cytokine distinctly modulates expression of phagocytic receptors, FcgR- and CD13-mediated phagocytosis, and ROS production..

Biotin deficiency is known to affect immune function in both humans and experimental animals. In this study, we determined the effect of biotin deficiency on 4-wk-old Balb/cAnN mice during 20 wk of experimentation. The growth rate of mice slowed significantly during the first 6 wk of consumption of a diet designed to induce biotin deficiency; thereafter, from weeks 7 to 20 there was progressive weight loss in the mice receiving the biotin-deficient diet. In the livers of biotin-deficient mice, the specific activities of two biotin-dependent enzymes--pyruvate carboxylase and propionyl-CoA carboxylase--decreased by as much as 75% and 80%, respectively, and in spleen lymphocytes the specific activities of these two enzymes decreased by 63% and 75%, respectively. With respect to the effects of biotin deficiency on the immune system, we observed statistically significant changes in both the absolute number of spleen cells and in the proportions of spleen cells carrying different phenotypic markers: after 16 wk the percentage of cells expressing surface immunoglobulin (sIg) decreased from 47% (control and supplemented) to 27% (deficient) and CD3+ cells increased from 42% (control and supplemented) to 54% (deficient). The mitogen-induced proliferation of spleen cells from deficient mice was lower than that of spleen cells from the control mice. These findings suggest that biotin could have an important role in lymphocyte maturation and responsiveness to stimulation, and consequently in the capacity of the immune system to respond to an antigenic challenge.