Role Of C-type Lectin Receptors Research Articles

Differing Expression and Potential Immunological Role of C-Type Lectin Receptors of Two Different Chicken Breeds against Low Pathogenic H9N2 Avian Influenza Virus.

Diverse immune responses in different chicken lines can result in varying clinical consequences following avian influenza virus (AIV) infection. We compared two widely used layer breeds, Lohmann Brown (LB) and Lohmann White (LW), to examine virus replication and immune responses against H9N2 AIV infection. The transcription profile in the spleen of H9N2-infected chickens was compared using a microarray. Confirmatory real-time RT-PCR was used to measure the expression of C-type lectin, OASL, and MX1 genes. Additionally, to investigate the role of chicken lectin receptors in vitro, two C-type lectin receptors (CLRs) were expressed in DF-1 cells, and the early growth of the H9N2 virus was evaluated. The LB chickens shed a lower amount of virus from the cloaca compared with the LW chickens. Different expression levels of C-type lectin-like genes were observed in the transcription profile, with no significant differences in OASL or MX gene expression. Real-time RT-PCR indicated a sharp decrease in C-type lectin levels in the spleen of H9N2-infected LW chickens. In vitro studies demonstrated that cells overexpressing CLR exhibited lower virus replication, while silencing of homeostatic CLR had no effect on AIV replication. This study demonstrated distinct immune responses to H9N2 avian influenza in LB and LW chickens, particularly with differences in C-type lectin expression, potentially leading to lower virus shedding in LB chickens.

The multiple roles of C-type lectin receptors in cancer

C-type lectin receptors are a family of immune response receptors that can bind with a broad repertoire of ligands. It can function as innative immune receptors to surveillance bacteria, fungi, and virus invasions. The expressions of C-type lectin receptors (CLRs) are found in different types of tumors. But the role of C-type lectin receptors in cancer is not fully elucidated. And the underlying mechanisms of CLRs in carcinogenesis and tumor development remained unknown. It is known that CLRs bind to the glycosylated antigen on the cancer cells, regulating cancer cell invasion, migration, and metastasis. Meanwhile, the recognition of tumor glycans by antigen-presenting cells can stimulate antitumor immune response and induce immune tolerance. Also, some types of CLRs can be used as diagnostic markers for tumor cells, suggesting that C-type lectin can function as a new tumor therapeutic target and potential biomarkers. Given the therapeutic potential of CLRs in tumor treatments and the emerging roles of CLR in the tumor hallmarks, the multiple roles of CLRs in cancer were summarized in this review.

C-type lectin receptor Dectin3 deficiency balances the accumulation and function of FoxO1-mediated LOX-1+ M-MDSCs in relieving lupus-like symptoms

Recent studies indicate that Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) can function as the signal of pattern recognition receptors, which play a pivotal role in the pathogenesis of the autoimmune disease. Systemic lupus erythematosus (SLE) is a classic autoimmune disease. Previous reports mainly focused on the potential role of TLRs in regulating the development of SLE, but little is known about the role of CLRs in the progression of SLE. Our previous studies showed that the inflammation-mediated accumulation of myeloid-derived suppressor cells (MDSCs) including granulocytic (G-MDSCs) and monocytic (M-MDSCs) participated in the pathogenesis of lupus. Mice deficient in Card9 (the downstream molecule of CLRs) were more susceptible to colitis-associated cancer via promoting the expansion of MDSCs. Whether the abnormal activation of CLRs regulates the expansion of MDSCs to participate in the pathogenesis of lupus remains unknown. In the present study, the expressions of CLRs were examined in both SLE patients and mouse models, revealing the expression of Dectin3 was positively correlated with SLEDAI. Dectin3 deficiency retarded the lupus-like disease by regulating the expansion and function of MDSCs. The mechanistic analysis revealed that Dectin3 deficiency promoted FoxO1-mediated apoptosis of MDSCs. Syk-Akt1-mediated nuclear transfer of FoxO1 increased in Dectin3-deficient MDSCs. Notedly, the accumulation of M-MDSCs mainly decreased in Dectin3−/− lupus mice, and the nuclear transfer of FoxO1 negatively correlated with the expression of LOX-1 on M-MDSCs. The silencing of FoxO1 expression in Dectin3−/− mice promoted the expansion of LOX-1+ M-MDSCs in vivo, and LOX-1+ M-MDSCs increased the differentiation of Th17 cells. Both LOX-1 expression on M-MDSCs and Dectin3 expression on MDSCs increased in patients with SLE. These data indicated that increased LOX-1+ M-MDSCs were related to the exacerbation of SLE development and might be potential target cells for the treatment of SLE.

Role of C-type Lectin Receptor to C.albicans on Promotion of Inflamantory Diseases

<p><em>In early 2010 there was a very rapid progress in the development of immunity to fungi, i.e the discovery of CLR. CLR is one of the PRR receptors found in immune cells that recognize the cell wall of fungi and then trigger a transduction signal that eventually provoke the production of various proinflamatory include IL1β, IL6, TNF α and induce polarization Th17. In the condition of infection the number of innate immune cells increases dramatically, lead to increasing of cytokines produced. Both cytokines and the cells that produce them enter the bloodstream. If there is unbalance level of pro and anti inflammatory cytokine, various inflammatory and/or autoimmune diseases can be occur. Unlike the focal concept infection, where the agent will cause disease if enters the blood vessels, through this concept a fungal infection at epithelium can lead to inflammatory diseases in other part of body without having to go through fungus</em></p><p><em> </em></p><p><strong><em>Keywords:</em></strong><em> C. albicans, CLR, Cytokine, Inflamatory Disease</em></p><p><strong><em> </em></strong></p><strong><em>Correspondence: </em></strong><em>Erna Sulistyani, Department of Oral Medicine, Faculty of Dentistry, Jember Bagian Penyakit Mulut, Fakultas Kedokteran Gigi, Universitas Jember, Kalimantan 37 Jember, Email: </em><a href="mailto:erna.sulistyani67@gmail.com"><em>erna.sulistyani67@gmail.com</em></a>

The CARD9-Associated C-Type Lectin, Mincle, Recognizes La Crosse Virus (LACV) but Plays a Limited Role in Early Antiviral Responses against LACV

La Crosse virus (LACV) is a mosquito-transmitted arbovirus and the main cause of virus-mediated neurological diseases in children. To date, little is known about the role of C-type lectin receptors (CLRs)—an important class of pattern recognition receptors—in LACV recognition. DC-SIGN remains the only well-described CLR that recognizes LACV. In this study, we investigated the role of additional CLR/LACV interactions. To this end, we applied a flow-through chromatography method for the purification of LACV to perform an unbiased high-throughput screening of LACV with a CLR-hFc fusion protein library. Interestingly, the CARD9-associated CLRs Mincle, Dectin-1, and Dectin-2 were identified to strongly interact with LACV. Since CARD9 is a common adaptor protein for signaling via Mincle, Dectin-1, and Dectin-2, we performed LACV infection of Mincle−/− and CARD9−/− DCs. Mincle−/− and CARD9−/− DCs produced less amounts of proinflammatory cytokines, namely IL-6 and TNF-α, albeit no reduction of the LACV titer was observed. Together, novel CLR/LACV interactions were identified; however, the Mincle/CARD9 axis plays a limited role in early antiviral responses against LACV.

Cell wall mannan of Candida krusei mediates dendritic cell apoptosis and orchestrates Th17 polarization via TLR-2/MyD88-dependent pathway

Dendritic cells (DCs) abundantly express diverse receptors to recognize mannans in the outer surface of Candida cell wall, and these interactions dictate the host immune responses that determine disease outcomes. C. krusei prevalence in candidiasis worldwide has increased since this pathogen has developed multidrug resistance. However, little is known how the immune system responds to C. krusei. Particularly, the molecular mechanisms of the interplay between C. krusei mannan and DCs remain to be elucidated. We investigated how C. krusei mannan affected DC responses in comparison to C. albicans, C. tropicalis and C. glabrata mannan. Our results showed that only C. krusei mannan induced massive cytokine responses in DCs, and led to apoptosis. Although C. krusei mannan-activated DCs underwent apoptosis, they were still capable of initiating Th17 response. C. krusei mannan-mediated DC apoptosis was obligated to the TLR2 and MyD88 pathway. These pathways also controlled Th1/Th17 switching possibly by virtue of the production of the polarizing cytokines IL-12 and IL-6 by the C. krusei mannan activated-DCs. Our study suggests that TLR2 and MyD88 pathway in DCs are dominant for C. krusei mannan recognition, which differs from the previous reports showing a crucial role of C-type lectin receptors in Candida mannan sensing.

Expression, Distribution, and Role of C-Type Lectin Receptors in the Human and Animal Middle Ear and Eustachian Tube: A Review.

Otitis media (OM) is a group of inflammatory diseases of the middle ear (ME), regardless of cause or pathological mechanism. Among the molecular biological studies assessing the pathology of OM are investigations into the expression of C-type lectin receptors (CLR) in the ME and Eustachian tube (ET). To date, nine studies have evaluated CLR expression in the ME and ET. The expression of individual CLRs in mammalian ME and ET varies by species and model of OM. Assessments have shown that the patterns of CLR expression in the ME and ET vary; that CLR expression may vary by type of OM; and that the distribution and levels of expression of CLRs may depend on the presence or absence of inflammation, with variations even within the same species and same tissue. Infection of the ME and ET with various pathogens is a common cause of all types of OM, with host responses to pathogens mediated initially by the innate immune system. CLRs are important factors in the innate immune system because they act as both adhesion molecules and as pathogen recognition receptors. The expression of CLRs in OM tissues suggests that CLRs are associated with the pathogenesis of various types of OM.

Genetic polymorphisms of C-type lectin receptors in Behcet\u2019s disease in a Chinese Han population

C-type lectin receptors (CLRs) have been demonstrated to be involved in several autoimmune diseases. The role of CLRs in Behcet’s disease (BD) is unknown and thus was the purpose of this study. A two-stage association study was carried out and a total of 766 BD patients and 1674 healthy controls were recruited. Genotyping of 14 SNPs of 13 genes in CLRs was carried out by iPLEX Gold genotyping or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The expression of mannose binding lectin 2 (MBL2) and killer cell lectin like receptor C4 (KLRC4) was measured by Real-time PCR. Significantly increased frequencies of the A allele as well as AA genotype of rs1800450 in MBL2 (Pc = 2.50 × 10−6, OR = 1.494; Pc = 2.24 × 10−6,OR = 2.899; respectively) and TT genotype of rs2617170 in KLRC4 (Pc = 2.53 × 10−6, OR = 1.695) and decreased frequencies of GG genotype of rs1800450 (Pc = 1.56 × 10−3, OR = 0.689) and C allele as well as CC genotype of rs2617170 (Pc = 2.05 × 10−9,OR = 0.664; Pc = 1.20 × 10−5, OR = 0.585; respectively) were observed in BD. Two variants, p.Gly54Asp (rs1800450) and p.Asn104Ser (rs2617170) affect MBL2 and KLRC4 protein stability and expression. Our study demonstrates that the MBL2/rs1800450 and KLRC4/rs2617170 are susceptibility factors for BD in a Chinese Han population.

The platelet‐activating receptor C‐type lectin receptor‐2 plays an essential role in liver regeneration after partial hepatectomy in mice

Background and aim The aim of the present study was to investigate the role of C-type lectin receptor (CLEC)-2 in liver regeneration following partial liver resection in mice. Materials and methods Irradiated chimeric mice transplanted with fetal liver cells from wild-type (WT) mice, CLEC-2-deleted (KO) mice or mice with CLEC-2 deleted specifically from platelets (flKO) were generated. Mice underwent 70% partial hepatectomy (PH). Immunohistochemical staining was performed to investigate the expression of the endogenous ligand for CLEC-2, podoplanin. The accumulation of platelets in the liver was also quantified. The hepatic expression of the IL-6/gp130 and STAT3, Akt and ERK1/2 was also examined. Results The liver/body weight ratio and expression of all cell proliferation markers were significantly lower in the flKO group than in the WT group. The expression of phosphorylated (p) Akt and pERK1/2 was similar in the WT and flKO groups. On the other hand, the expression of pSTAT3 and IL-6 was significantly stronger in the WT group than in the flKO group. The expression of podoplanin was detected in the hepatic sinusoids of both groups. However, the extent to which platelets accumulated in hepatic sinusoids was significantly less in the flKO group than in the WT group. Conclusion CLEC-2 was involved in hepatic regeneration after liver resection and CLEC-2-related liver regeneration was attributed to the interaction between platelets and sinusoidal endothelial cells.

High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR

Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. In addition, these N-linked glycoconjugates inhibited the DCs maturation induced by LPS. The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs.

C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia.

Among various innate immune receptor families, the role of C-type lectin receptors (CLRs) in lung protective immunity against Streptococcus pneumoniae (S. pneumoniae) is not fully defined. We here show that Mincle gene expression was induced in alveolar macrophages and neutrophils in bronchoalveolar lavage fluids of mice and patients with pneumococcal pneumonia. Moreover, S. pneumoniae directly triggered Mincle reporter cell activation in vitro via its glycolipid glucosyl-diacylglycerol (Glc-DAG), which was identified as the ligand recognized by Mincle. Purified Glc-DAG triggered Mincle reporter cell activation and stimulated inflammatory cytokine release by human alveolar macrophages and alveolar macrophages from WT but not Mincle KO mice. Mincle deficiency led to increased bacterial loads and decreased survival together with strongly dysregulated cytokine responses in mice challenged with focal pneumonia inducing S. pneumoniae, all of which was normalized in Mincle KO mice reconstituted with a WT hematopoietic system. In conclusion, the Mincle-Glc-DAG axis is a hitherto unrecognized element of lung protective immunity against focal pneumonia induced by S. pneumoniae.

Systems Level Dissection of Candida Recognition by Dectins: A Matter of Fungal Morphology and Site of Infection.

Candida albicans is an ubiquitous fungal commensal of human skin and mucosal surfaces, and at the same time a major life-threatening human fungal pathogen in immunocompromised individuals. Host defense mechanisms rely on the capacity of professional phagocytes to recognize Candida cell wall antigens. During the past decade, the host immune response to Candida was dissected in depth, highlighting the essential role of C-type lectin receptors, especially regarding the power of the Dectins’ family in discriminating between the tolerated yeast-like form of Candida and its invading counterpart, the hyphae. This review focuses on the immuno-modulatory properties of the Candida morphologies and their specific interactions with the host innate immune system in different body surfaces.

Antibacterial and pro-resolving mechanisms in lung diseases: role of C-type lectin receptors (INM2P.430)

Abstract Lower respiratory tract infection with bacteria can lead to sepsis development, a complex immune disorder with systemic hyperinflammation. There are currently no effective therapies for sepsis. To understand the function of specific pulmonary components in regulation of immune responses in this immune disorder, we utilize an acute pulmonary bacterial infection model of Klebsiella pneumoniae (KPn). Nosocomial infections with this opportunistic pathogen account for 5-20% of Gram-negative sepsis cases. C-type lectin receptors (CLRs), expressed mainly by myeloid cells, can shape immune responses in diverse pathological conditions. However, their role in development of pneumonic sepsis is unknown. Our preliminary analysis of a panel of CLRs showed an upregulated expression of two CLRs, Clec4d and Clec4e in the lungs of KPn infected mice. While the wild-type mice were able to resolve a sublethal pneumonic KPn infection, the Clec4d-/- and Clec4e-/- mice displayed increased susceptibility with a progressive increase in bacterial burden, hyperinflammatory response and massive accumulation of neutrophils in lungs. Importantly, we show that coordinated function of Clec4d and Clec4e in neutrophils during bacterial pneumonia, and in a chronic lung disease, leads to control of bacterial growth and hyperinflammation by regulating phagocytosis and efferocytosis (clearance of dead cells). Our studies provide novel insights into regulation of inflammatory derangements in immune disorders.

Ly49 and C-type lectin receptors on dendritic cells regulate T-cell differentiation as co-stimulatory molecules

The C-type lectin receptors (CLRs) expressed on dendritic cells (DCs) participate in T-cell polarization by recognizing pathogen-associated molecular patterns and activating signaling pathways for cytokine production. In addition, some CLRs expressed on DCs function as co-stimulatory molecules via recognition of endogenous ligands on T cells and regulate proliferation and/or differentiation of T cells. We recently showed that killer cell lectin-like receptor Ly49s3 is expressed in rat thymic DCs and recognizes MHC class I molecules on T cells, for differentiation into naturally occurring regulatory T cells (nTregs). Upon binding to MHC class I molecules on T cells, Ly49s3 seems to stimulate signal transduction pathway(s) leading to up-regulation of the MHC class II genes and then functions as a co-stimulatory molecule. The signaling pathway(s) is supposed to involve Dap12, Syk/Zap70, Lat, Plc-gamma, PKC, PU.1 and C2ta proteins to attain MHC class II expression. Other than Ly49s3, Ly49Q and Ly49B have been shown to be expressed in myeloid cells including DCs and macrophages, raising the possibility that they may be involved in the regulation of T-cell differentiation through recognition of MHC class I molecules on T cells. In humans, immunoglobulin (Ig)-like receptors binding to MHC class I molecules take the place of Ly49 receptors. Among them, expression of the KIR2DL4 gene has been reported to be induced in antigen-presenting cells, although its biological significance is obscure, and immunoglobulin-like transcript 4 (ILT4) expressed in DCs has been shown to down-regulate expression of MHC class II molecules on the same cells, upon binding to MHC class I molecules. They may also be involved in regulation of T-cell differentiation. Some other CLRs are expressed on DCs and possibly function as co-stimulatory molecules. For example, dectin-1, dectin-2 and Dcal-1 have been shown to promote T-cell proliferation, Treg differentiation and IL-4 production of T cells, respectively, through binding to unidentified ligands on T cells. DC-Sign, which recognizes ICAM3 on T cells, is also suggested to be involved in T-cell differentiation. Further investigation of the functional roles of CLRs on DCs will provide insight into the regulatory mechanisms of T-cell differentiation, essential processes for regulating immune responses.

C-type lectin receptors mRNA expression in patients with otitis media with effusion

ObjectiveThe role of C-type lectin receptor, a type of pattern recognition receptor, in otitis media with effusion (OME) is unclear. We assayed the levels of expression of C-type lectin receptor mRNA in children with OME and evaluated its relationship to the presence of bacteria, accompanying diseases, and characteristics of exudates. Subjects and MethodsThe study population consisted of 73 children with OME who had undergone ventilating tube insertion. The levels of expression of Dectin-1, MR1, MR2, DC-SIGN, Syk, Card-9, Bcl-10, Malt-1, Src, Dec-205, Galectin-1, Tim-3, Trem-1, and DAP-12 mRNA in middle ear effusion were determined by real-time PCR. The level of expression of each mRNA was correlated with the presence of bacteria, accompanying diseases, and exudates characteristics. ResultsThe levels of expression of C-type lectin receptor mRNAs were not associated with bacterial presence or exudates characteristics (p>0.05 each). Levels of expression, however, were significantly higher in patients with sinusitis, adenoid vegetation or adenoiditis, and allergic rhinitis (p<0.05 each). ConclusionsLevels of expression of C-type lectin receptor mRNA may be associated with the pathogenesis of OME, being significantly higher in patients with than without accompanying sinusitis, adenoid vegetation or adenoiditis, and allergic rhinitis.

The role of C-type lectin receptors in immune homeostasis

C-type lectin receptors (CLRs) are important pathogen pattern recognition molecules that recognize carbohydrate structures. Upon ligand binding, CLRs induce a variety of cellular responses, such as respiratory burst, production of cytokines and chemokines, and consequently shaping the adaptive immune responses. Recent frontier studies have demonstrated that CLRs play a significant role in development of anti-inflammatory immune responses and maintenance of host immune-homeostasis. In this review we describe the major CLRs involved in production of IL-10 by immune-related cells and functional maturation of regulatory T cells. In addition, we discuss the potential role of CLRs signaling in regulating intestinal immune-homeostasis and inflammation. Further understanding of the precise role for these receptors on immunoregulatory cells will provide unexpected opportunities for developing new therapies for inflammatory diseases.

Signaling via an adapter molecule CARD9 is essential for the host defense to infection with Cryptococcus neoformans (55.5)

Abstract CARD9 is a critical adaptor molecule signaling for NF-κB activation triggered via C-type lectin receptors (CLRs), which recognize carbohydrate structures of microbes. Cryptococcus neoformans, a yeast-like fungus is recognized by some CLRs, such as mannose receptor or DC-SIGN, whereas the role of CLRs or CARD9 in the host defense to this infection remains to be elucidated. In this study, we analyzed the role of CARD9 in the protective immune response to C. neoformans infection. C57BL/6 and CARD9KO mice were infected intratracheally with C. neoformans (B3501). The number of live microbes, histopathological findings and cytokine synthesis in lungs and the cytokine response of paratracheal lymph node (LN) cells upon antigenic re-stimulation were evaluated. CARD9KO mice were highly susceptible to infection with C. neoformans, as shown by increased number of live microbes in lungs compared to control, which was associated with less marked granulomatous response and remarkable multiplication of yeast cells in the alveolar spaces. Expression of RORγt and IL-17A mRNA and intracellular expression of IL-17A by T, NKT and γδ T cells were strongly attenuated in the lungs of CARD9KO mice. IL-17A production by the re-stimulated LN cells was mostly abrogated in these mice. By contrast, Th1-cytokine response was not much affected. These results suggest that CARD9 is a key molecule in the Th17 response to C. neoformans, which is associated with the host defense against this infection.

Phospholipase Cγ2 (PLCγ2) Is Key Component in Dectin-2 Signaling Pathway, Mediating Anti-fungal Innate Immune Responses

C-type lectin receptors (CLRs) such as Dectin-2 function as pattern recognition receptors to sense fungal infection. However, the signaling pathways induced by these receptors remain largely unknown. Previous studies suggest that the CLR-induced signaling pathway may utilize similar signaling components as the B cell receptor-induced signaling pathway. Phospholipase Cγ2 (PLCγ2) is a key component in B cell receptor signaling, but its role in other signaling pathways has not been fully characterized. Here, we show that PLCγ2 functions downstream of Dectin-2 in response to the stimulation by the hyphal form of Candida albicans, an opportunistic pathogenic fungus. Using PLCγ2- and PLCγ1-deficient macrophages, we found that the lack of PLCγ2, but not PLCγ1, impairs cytokine production in response to infection with C. albicans. PLCγ2 deficiency results in the defective activation of NF-κB and MAPK and a significantly reduced production of reactive oxygen species following fungal challenge. In addition, PLCγ2-deficient mice are defective in clearing C. albicans infection in vivo. Together, these findings demonstrate that PLCγ2 plays a critical role in CLR-induced signaling pathways, governing antifungal innate immune responses.

Highly glycosylated tumour antigens: interactions with the immune system

A common phenotypic change in cancer is a dramatic transformation of cellular glycosylation. Functional studies of particular tumour-associated oligosaccharides are difficult to interpret conclusively, but carbohydrate-binding proteins are likely to contribute to progression of the tumour. This review discusses the potential role of CLRs (C-type lectin receptors), expressed by antigen-presenting cells of the immune system, in tumour recognition and immune modulation. Studies in recent years have provided significant insight into the immunomodulatory function of CLR during infections, but their role in cancer remains elusive; some strongly bind tumour cells and antigens, indicating participation in malignancy. The potential to use recombinant CLR as diagnostic tools will also be discussed.

Bitter-sweet symphony: defining the role of dendritic cell gp120 receptors in HIV infection.

Dendritic cells (DC) are believed to be one of the first cell types infected during HIV transmission. Recently a single C-type lectin receptor (CLR), DC-SIGN, has been reported to be the predominant receptor on monocyte derived DC (MDDC) rather than CD4. The role of other CLRs in HIV binding and HIV binding by CLRs on other types of DC in vivo is largely unknown. Review HIV binding to DC populations, both in vitro and in vivo, in light of the immense interest of a recently re-identified CLR called DC-SIGN. From recent work, it is clear that immature MDDC have a complex pattern of HIV gp120 binding. In contrast to other cell types gp120 has the potential to bind to several receptors on DC including CD4 and several types of C type lectin receptor, not just exclusively DC-SIGN. Given the diverse types of DC in vivo future work will need to focus on defining the receptors for HIV binding to these different cell types. Mucosal transmission of HIV in vivo targets immature sessile DCs, including Langerhans cells which lack DC-SIGN. The role of CLRs and DC-SIGN in such transmission remains to be defined.