The recognition of carbohydrate moieties by cells of the innate immune system is emerging as an essential element in antifungal immunity, but despite the number and diversity of lectins expressed by innate immune cells, few carbohydrate receptors have been characterized. Mincle, a C-type lectin, is expressed predominantly on macrophages, and is here shown to play a role in macrophage responses to the yeast Candida albicans. After exposure to the yeast in vitro, Mincle localized to the phagocytic cup, but it was not essential for phagocytosis. In the absence of Mincle, production of TNF-α by macrophages was reduced, both in vivo and in vitro. In addition, mice lacking Mincle showed a significantly increased susceptibility to systemic candidiasis. Thus, Mincle plays a novel and nonredundant role in the induction of inflammatory signaling in response to C. albicans infection.

Ras signaling appears to be mediated in part by transcription factors that belong to the ets gene family. To identify downstream targets for the Ras signal transduction pathway, we have used Ras-transformed mouse fibroblasts to isolate a new member of the ets gene family, net. Net has sequence similarity in three regions with the ets factors Elkl and SAP1, which have been implicated in the serum response of the fos promoter. Net shares various properties with these proteins, including the ability to bind to ets DNA motifs through the Ets domain of the protein and form ternary complexes with the serum response factor SRF on the fos serum response element, SRE. However, Net differs from Elkl and SAP1 in a number of ways. The pattern of net RNA expression in adult mouse tissues is different. Net has negative effects on transcription in a number of assays, unlike Elkl. Strikingly, Ras, Src, and Mos expression switch Net activity to positive. The study of Net should help in understanding the interplay between Net and other members of the Elk subfamily and their contribution to signal transduction through Ras to the nucleus.

Background: C-type lectins play important roles in immunity and homeostasis.Results: CLECSF8 is expressed on neutrophils and monocytes and can mediate phagocytosis, the respiratory burst and inflammatory cytokine production, in part through association with a novel adaptor.Conclusion: CLECSF8 can trigger cellular activation.Significance: This study identifies a novel C-type lectin that can control immune cell function.

The ternary complex factors (TCFs) Net, Elk-1 and Sap-1 regulate immediate early genes through serum response elements (SREs) in vitro, but, surprisingly, their in vivo roles are unknown. Net is a repressor that is expressed in sites of vasculogenesis during mouse development. We have made gene-targeted mice that express a hypomorphic mutant of Net, Netd, which lacks the Ets DNA-binding domain. Strikingly, homozygous mutant mice develop a vascular defect and up-regulate an immediate early gene implicated in vascular disease, egr-1. They die after birth due to respiratory failure, resulting from the accumulation of chyle in the thoracic cage (chylothorax). The mice have dilated lymphatic vessels (lymphangiectasis) as early as E16.5. Interestingly, they express more egr-1 in heart and pulmonary arteries at E18.5. Net negatively regulates the egr-1 promoter and binds speci®-cally to SRE-5. Egr-1 has been associated with pathologies involving vascular stenosis (e.g. atherosclerosis), and here egr-1 dysfunction could possibly be associated with obstructions that ultimately affect the lymphatics. These results show that Net is involved in vascular biology and egr-1 regulation in vivo. Keywords: egr-1/Elk-3/ERP/Net/Sap-2 IntroductionThe ternary complex factors (TCFs) form a subfamily of Ets-domain transcription factors. The three TCFs, Elk-1, Sap-1 and Net/Sap-2/Erp/Elk-3 (Price et al., 1996;Wasylyk et al., 1998), have four conserved domains, A±D. A is the Ets DNA-binding domain (DBD). The B-box interacts with the serum response factor (SRF). C is a transcriptional activation domain that is stimulated by mitogen-activated protein (MAP) kinase phosphorylation. The D-domain is a MAP kinase-binding site and a nuclear localization signal. The TCFs are nuclear mediators of cellular responses to the activation of MAP kinase pathways. Net differs from the other TCFs in that in basal conditions, in which MAP kinases are not activated, it strongly inhibits transcription. Repression is mediated by two domains, the NID (Maira et al., 1996) and the CID (Criqui-Filipe et al., 1999). The TCFs form ternary complexes with SRF on serum response elements (SREs) of immediate early gene promoters, such as c-fos, egr-1 and jun-B. The SRE is constitutively occupied by factors, and extracellular signals are thought to lead to both phosphorylation of the complex and changes in its composition due to the exchange of TCFs.The in vivo role of the TCFs is poorly understood. They may regulate the expression of immediate early genes in response to various inductive stimuli. The TCFs are expressed in many cell types and tissues (Giovane et al., 1994;Lopez et al., 1994;Magnaghi-Jaulin et al., 1996;Nozaki et al., 1996;Sgambato et al., 1998), but their precise in vivo expression patterns are not well known. Net is expressed during mouse development at E7.5±8.5 in developing vascular primordia, including the yolk sac blood islands, allantoic vessels, heart endocardium and dorsal aortae (Ayadi et al., 2001). Vascular endothelial cell expression persists ...