The human β‐glucan receptor is widely expressed and functionally equivalent to murine Dectin‐1 on primary cells

Willment, Janet A.; Marshall, Andrew S J; Reid, Delyth M.; Williams, David L.; Wong, Siew Yee; Gordon, Siamon; Brown, Gordon D.

doi:10.1002/eji.200425725

Cited by 234 publications

(203 citation statements)

References 53 publications

(62 reference statements)

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“…This expression profile of MICL is similar to that of the related receptor, beta-glucan receptor/ Dectin-1, found in the same gene cluster [21], and is largely consistent with previous transcript analyses [14,16,17], although some differences were noted, as discussed above. MICL has also been proposed to be expressed on NK cells, based on the ability of an Fc-MICL fusion protein to inhibit cytotoxicity [16].…”

Section: Discussionsupporting

confidence: 90%

“…Further analysis of MICL expression on the recruited granulo- cytes, demonstrated that down-regulation of this receptor was concomitant with the reduction in CD16 expression, as described above. This down-regulation of MICL was specific, as other receptors on these cells, including Dectin-1 and EMR1, were regulated differently ( [21] and data not shown). At 24 h, when some recruited granulocytes still maintained CD16 expression, two subpopulations (CD16 + MICL + and CD16 -MICL -) were easily definable, although some background nonspecific staining was observed with the CD16 isotype control (Fig.…”

Section: Micl Expression During Inflammation In Vivomentioning

confidence: 87%

“…Adherent monocytes, isolated as described previously [21], were cultured in X-VIVO medium (BioWhittaker) with 1% heatinactivated autologous serum for differentiation into MU, or cultured in RPMI with 10% heat-inactivated FCS, 50 ng/mL GM-CSF and 25 ng/mL IL-4 (R&D Systems) to produce DC. Activation/maturation of immature DC (day 6) was achieved with the addition of 1 lg/mL LPS for 48 h.…”

Section: Cells and Cell Culturementioning

confidence: 99%

“…Antibodies used in these experiments included: HB3 and HB3-biotin, GE2 and GE2-biotin [21], CD4 (CFAR), CD14-FITC (BD PharMingen), CD16 (Serotec), CD16-PE (BD PharMingen), CD56-PE (BD PharMingen), CD19-PE (BD PharMingen), DC-SIGN-FITC (BD PharMingen), CD19-FITC (Caltag), CD1c (Serotec), BDCA2 [53], CD8-PE (Serotec), CD83-PE (Serotec), CD86-PE (Serotec), CD3-FITC (Serotec), CD11b-FITC (Serotec), HLA-DR-FITC (Serotec), CD15-FITC (Serotec), and irrelevant unlabelled or biotin-, PE-or FITC-labelled mouse or rat IgG1 (including D1.3; a gift from L. Martinez-Pomares, Oxford University, Oxford, UK), IgM (Serotec) and IgG2b (ECACC) control antibodies. Biotinylated antibodies were detected using streptavidin-allophycocyanin (BD PharMingen).…”

Section: Antibodies and Flow Cytometrymentioning

confidence: 99%

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Human MICL (CLEC12A) is differentially glycosylated and is down‐regulated following cellular activation

Willment¹,

Pyż²,

Dennehy³

et al. 2006

Eur J Immunol

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C-type lectins are the most diverse and prevalent lectin family in immunity. Particular interest has recently been attracted by the C-type lectin-like receptors on NK cells, which appear to regulate the activation/inhibitory balance of these cells, controlling cytotoxicity and cytokine production. We previously identified a human C-type lectin-like receptor, closely related to both the beta-glucan receptor and the lectin-like receptor for oxidized-LDL, named MICL (myeloid inhibitory C-type lectin-like receptor), which we had shown using chimeric analysis to function as an inhibitory receptor. Using a novel MICL-specific monoclonal antibody, we show here that human MICL is expressed primarily on myeloid cells, including granulocytes, monocytes, macrophages, and dendritic cells. Although MICL was highly N-glycosylated in primary cells, the level of glycosylation was found to vary between cell types. MICL surface expression was down-regulated during inflammatory/activation conditions in vitro, as well as during an in vivo model of acute inflammation, which we characterize here. This suggests that human MICL may be involved in the control of myeloid cell activation during inflammation. IntroductionIn order to execute their immune (and non-immune) functions, leukocytes must interact with a broad range of endogenous and exogenous ligands and must be able to respond to these interactions appropriately. This requires a wide and flexible, yet specific and regulated, repertoire of cell surface molecules. One large family of such molecules, which are particularly important to immunity, are the C-type lectin and lectin-like receptors. C-type lectin-like receptors were first identified as dimeric molecules on NK cells. On these cells, much attention has been drawn toward their ability to regulate the balance between cellular activation and inhibition, such as cytotoxicity and cytokine production. This is achieved through signalling via intracellular ITIM present in the cytoplasmic tails of these receptors or via ITAM, of which the majority are located in the cytoplasmic tails of associated molecules, such as DAP12. The study of these activationand inhibitory NK cell receptorshas generated a number of interesting hypotheses, including immune privilege [1], the recognition of 'missing self', 'non-self' and 'induced self' [2][3][4][5], as well elucidating the underlying mechanisms of some of the immune responses to viruses [6] and malignancy [7]. Others and we have demonstrated that C-type lectinlike receptors are not restricted to NK cells, but are expressed by many other cell types including myeloid cells [8][9][10]. This introduces the novel concept that the myeloid paralogs of NK cell receptors might govern myeloid cell activation/inhibition in the same manner as those on NK cells. The genes of most C-type lectin-like molecules are located within the 'natural killer complex' (NKC), but many of those expressed by myeloid and other cells are found in a distinct cluster of genes within the NKC [10]. This cluster includes Decti...

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Section: Discussionsupporting

confidence: 90%

Section: Micl Expression During Inflammation In Vivomentioning

confidence: 87%

Section: Cells and Cell Culturementioning

confidence: 99%

Section: Antibodies and Flow Cytometrymentioning

confidence: 99%

See 2 more Smart Citations

Human MICL (CLEC12A) is differentially glycosylated and is down‐regulated following cellular activation

Willment¹,

Pyż²,

Dennehy³

et al. 2006

Eur J Immunol

Self Cite

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“…There is a difference in the structure and function of Dectin-1 in susceptible B6 mice and resistant DBA/2 mice that is based on alternative splicing of the encoding gene, Clec7a [59]. That gene is also alternatively spliced in human cells [62,63], but there are no studies on how that differential splicing affects the human response to spherules.…”

Section: Immunologymentioning

confidence: 99%

Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity

Kirkland

Fierer

2018

Virulence

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Coccidioides immitis and C. posadasii are two highly pathogenic dimorphic fungal species that are endemic in the arid areas of the new world, including the region from west Texas to southern and central California in the USA that cause coccidioidomycosis (also known as Valley Fever). In highly endemic regions such as southern Arizona, up to 50% of long term residents have been infected. New information about fungal population genetics, ecology, epidemiology, and host-pathogen interactions is becoming available. However, our understanding of some aspects of coccidioidomycosis is still incomplete, including the extent of genetic variability of the fungus, the genes involved in virulence, and how the changes in gene expression during the organism’s dimorphic life cycle are related to the transformation from a free-living mold to a parasitic spherule. Unfortunately, efforts to develop an effective subunit vaccine have not yet been productive, although two potential live fungus vaccines have been developed.

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Macrophage Receptors and Innate Immunity: Insights from Dectin‐1

Brown

2006

Innate Immunity to Pulmonary Infection

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The innate ability of macrophages to induce an immune response to pathogens is dependent upon germline encoded pattern recognition receptors which recognise conserved microbial structures. These receptors not only mediate pathogen recognition, but promote microbial uptake and killing and the induction of infl ammatory responses. Although the recently described Toll-like receptors (TLR) have been shown to play a central role in mediating the intracellular signals involved, the non-TLRs also have important functions in these processes. Once such receptor is Dectin-1, a myeloid expressed signalling C-type lectin-like receptor which is involved in the innate recognition of fungal pathogens. Dectin-1 can induce a variety of cellular responses, including phagocytosis, the respiratory burst and cytokine production. These responses are mediated through novel signalling pathways induced from the cytoplasmic immuno-receptor tyrosine based activation-like motif of the receptor. Although the in vivo role of Dectin-1 has still to be fully elucidated, there is emerging evidence that this receptor plays a role in the infl ammatory response to pulmonary fungal pathogens and that it is involved in certain autoimmune and respiratory diseases.

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The human β‐glucan receptor is widely expressed and functionally equivalent to murine Dectin‐1 on primary cells

Cited by 234 publications

References 53 publications

Human MICL (CLEC12A) is differentially glycosylated and is down‐regulated following cellular activation

Human MICL (CLEC12A) is differentially glycosylated and is down‐regulated following cellular activation

Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity

Macrophage Receptors and Innate Immunity: Insights from Dectin‐1

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