| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-Glucan Receptor (Dectin-1) in the Nonopsonic Recognition of Yeast by Specific Macrophages1
* Sir William Dunn School of Pathology, Oxford University, South Parks Road, Oxford, United Kingdom; and
Department of Surgery, James H. Quillen College of Medicine, Johnson City, TN 37614
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResults and DiscussionReferences |
|---|
-glucan receptor Dectin-1 (GR) was the major nonopsonic -glucan receptor on macrophages (M
) for the yeast-derived particle zymosan. However, on resident peritoneal M, we identified an additional mannan-inhibitable receptor for zymosan that was distinct from the M mannose receptor (MR). In this study, we have studied the mannose-binding potential of murine M and identified the dendritic cell-specific ICAM-3-grabbing nonintegrin homolog, SIGN-related 1 (SIGNR1), as a major MR on murine resident peritoneal M. Both SIGNR1 and GR cooperated in the nonopsonic recognition of zymosan by these M. When SIGNR1 was introduced into NIH3T3 fibroblasts or RAW 264.7 M, it conferred marked zymosan-binding potential on these cells. However, in the nonprofessional phagocytes (NIH3T3), SIGNR1 was found to be poorly phagocytic, suggesting that other receptors such as GR may play a more dominant role in particle internalization on professional phagocytes. Binding of zymosan to RAW 264.7 M expressing SIGNR1 resulted in TNF-
production. Treatment of RAW 264.7 M expressing SIGNR1, which express low levels of GR, with -glucans had little effect on binding or TNF- production, indicating that there was no absolute requirement for GR in this process. These studies have identified SIGNR1 as a major MR for fungal and other pathogens present on specific subsets of M. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResults and DiscussionReferences |
|---|
-glucan receptor (GR)3 (1) and demonstrated that it was a major macrophage (M) receptor for the nonopsonic recognition of yeast (2). It is predominantly expressed on the surface of cells of the monocyte/M lineage, dendritic cells, and a subset of T cells (3). Interestingly, murine M exhibited some heterogeneity in the expression of GR, with high surface expression particularly evident on alveolar M (3), which are constantly exposed to fungal-derived material. The human GR homolog has also been identified (4, 5, 6, 7) and recognizes -glucans (6). More recently, we have been able to show that Dectin-1 is required in conjunction with Toll-like receptor 2 for the induction of TNF- production in response to zymosan recognition (8). These studies have established GR as a major pattern recognition receptor for the appropriate recognition and response to fungal infection.
Our examination of the nonopsonic recognition of zymosan by murine M led to the identification of an additional mannan-inhibitable receptor for the nonopsonic recognition of zymosan on the surface of resident peritoneal M (3). The heterogeneous expression of this receptor could represent the mannan-inhibitable receptor on peritoneal M described for Saccharomyces cerevisiae, zymosan, and Leishmania donovani promastigotes (9, 10, 11). Although at the time this activity was ascribed to the M mannose receptor (MR), we demonstrated with the aid of novel mAb that the expression of the M MR was inconsistent with this hypothesis (3). Candidates for this activity were the murine homologs of dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) (12, 13, 14) and DC-SIGNR (14, 15), which now have well-established mannose-binding credentials (14). The mouse has five homologs of DC-SIGN(R) (16), and one of these homologs has been shown to be expressed by select M, and possess mannose-binding activities (17, 18). Another candidate, Endo180, is an additional member of the MR family, which has similar ligand specificity to the M MR (19, 20).
In this study, we demonstrate that the uncharacterized mannan-inhibitable receptor on peritoneal M is SIGN-related 1 (SIGNR1), the murine homolog of DC-SIGNR. SIGNR1 is involved in the nonopsonic recognition of the yeast-derived particle zymosan (exhibiting additive cooperation with GR), facilitates the M TNF- response, and contributes to the recognition of the human pathogen Candida albicans but is poorly phagocytic in isolation.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResults and DiscussionReferences |
|---|
All mice used in this study were C57BL/6J or BALB/c and between 8 and 12 wk at the time of study. Primary cells were isolated as previously described (3). Primary M were cultured in RPMI 1640 (Invitrogen, Paisley, U.K.) supplemented with 10% heat-inactivated FCS, 100 U/ml penicillin, 0.1 mg/ml streptomycin, and 2 mM L-glutamine. NIH3T3 (American Type Culture Collection, Manassas, VA) and RAW 264.7 (American Type Culture Collection) were maintained in DMEM (Invitrogen) supplemented as above.
Isolation of RNA and RT-PCR analysis
Peritoneal cells were enriched by overnight adherence to tissue culture plastic. This process is known not to alter the presence of the mannan-inhibitable zymosan receptor on murine M (3). Isolation of total RNA and cDNA synthesis was performed as previously described (3). Primers for specific cDNA amplification were as follows: DC-SIGN, 5'-CATGAGTGATTCTAAGGAA-3' and 5'-TCACTTGCTAGGGCAGGAAG-3'; SIGNR1, 5'-ACCATGAGTGACTCCACAGAA-3' and 5'-CTAGCCTTCAGTGCATGGGG-3'; and 2-microglobulin, 5'-TGACCGGCTTGTATGCTATC-3' and 5'-CAGTGTGAGCCAGGATATAG-3'.
Retroviral transduction of NIH3T3 and RAW 264.7
To obtain stable SIGNR1-expressing NIH3T3 fibroblasts (NIH3T3-SIGNR1) and RAW 264.7 M (RAW-SIGNR1), the SIGNR1 cDNA (a gift from Dr. T. Geijtenbeek (Vrije Universiteit Medical Centre, Amsterdam, The Netherlands)) was subcloned into the retroviral vector pFB(neo) (Stratagene, La Jolla, CA). NIH3T3-SIGNR1, RAW-SIGNR1, and GR-expressing NIH3T3 fibroblasts (NIH3T3-GR) transductants were generated as previously described (2, 6).
Carbohydrates and mannose-binding assays
Synthetic biotinylated polymeric mannose ligand (Man-PAA-Bio) was obtained from Lectinicity (Munich, Germany). Mannan (from S. cerevisiae), laminarin (from Laminaria digitata), and monosaccharides were purchased from Sigma-Aldrich (St. Louis, MO). Glucan phosphate was produced as previously described (21).
For the assessment of surface mannose-binding activity on murine M, freshly isolated cells were washed twice with ice-cold wash solution (0.5% (w/v) BSA, 2 mM NaN3 in HBSS), and typically 0.5–1 x 106 cells per assay were blocked with 5% rabbit serum and 10 µg/ml 2.4G2 (anti-Fc
RII and -III) in the wash solution for 30 min at 4°C. After blocking, the cells were incubated with 10 µg/ml Man-PAA-Bio on ice in the same wash buffer. FITC-labeled F4/80 was included for the identification of M. After 1 h on ice, cells were washed twice with the same wash solution, and Man-PAA-Bio was detected with streptavidin-allophycocyanin (BD PharMingen, San Diego, CA) in wash buffer. Cells were washed three times with wash solution before analysis, and M were identified by flow cytometry, gating on F4/80+ cells.
Nonopsonic binding assays
For nonopsonic binding assays, a modification of our earlier assays (1, 2, 3) was developed for the analysis of freshly isolated cells. Freshly isolated peritoneal cells or subconfluent NIH3T3, which were lifted by scraping in 5 mM EDTA in PBS, were washed twice in ice-cold wash solution (see Carbohydrates and mannose-binding assays). A total of 2 x 105 peritoneal cells (1 x 105 NIH3T3) were placed in 96-well V-bottom bacterial plastic plates. Inhibitors (carbohydrates, Abs, or EDTA) were added (final concentrations stated where appropriate) and incubated on ice for 20 min before the addition of FITC-labeled zymosan (Molecular Probes, Eugene, OR), heat-killed C. albicans, or heat-killed Mycobacterium tuberculosis (a particle:cell ratio of 5:1 (25:1 for NIH3T3) was used). The cells and test particles were brought into contact by centrifugation at 350 x g for 5 min and left for 1 h on ice before resuspension and fixation in 1% formaldehyde. M in mixed cultures were identified by flow cytometry by F4/80 expression or their characteristic forward scatter/side scatter and autofluorescent profiles. Particle binding was identified by the acquisition of FITC labeling (see Flow cytometry).
Results from binding assays were either expressed as a percentage of the cells present that had bound to the test particle or as a relative binding index, to gain a more accurate estimate of the total number of particles bound to these cells. The binding index is expressed as the percentage of cells interacting with particles multiplied by the mean fluorescent intensity (MFI) of those cells. A relative binding index was obtained by normalizing results to the mean binding of untreated M or the mean of the transfected cells with the highest binding, both of which were assigned a binding index of 100.
Phagocytosis assays
NIH3T3-SIGNR1 or NIH3T3-GR were seeded at 2.5 x 105 cells/well in six-well dishes the day before assay. As a phagocytosis control, some cells were treated with 2 µM cytochalasin D (Sigma-Aldrich) 60 min before and throughout the assay. Plates were cooled on ice for 20 min, and then FITC-labeled zymosan (20 particles/cell) in ice-cold medium was added to each well, settled by gravity, and left for 60 min. After this time, unbound particles were removed by three washes with ice-cold medium, the medium was replaced, and the cells were returned to 37°C (5% CO2) for 60 min to allow phagocytosis to occur. Plates were then returned to ice, where they remained while they were stained in situ for the presence of bound zymosan on the outside of the cells.
For detection of external zymosan, cells were first blocked for 30 min with ice-cold 5% (v/v) goat serum and 0.5% (w/v) BSA in HBSS (containing Ca2+ and Mg2+). The block was replaced with a rabbit polyclonal anti-zymosan Ab (Molecular Probes) diluted 1/1000 in block for 1 h on ice. The anti-zymosan Abs are unable to bind to zymosan particles that have been internalized. The cells were washed three times with blocking solution, and an allophycocyanin-labeled goat anti-rabbit IgG (Molecular Probes) was added at a 1/200 dilution for a further 45 min. Cells were again washed three times with ice-cold blocking buffer and then detached by pipetting with HBSS before being fixed with 2% formaldehyde.
Flow cytometry
Flow cytometry was performed exactly as previously described (3). The labeled mAbs F4/80-PE/FITC/biotin (anti-F4/80), 5C6-FITC (anti-CD11b), and biotinylated mouse anti-rat IgM were obtained from Serotec (Oxford, U.K.). mAb ERTR9 (anti-SIGNR1) was obtained from DPC Biermann (Bad Nauheim, Germany), and control rat IgM was obtained from (BD PharMingen). mAb 2A11 (rat IgG2b, anti-GR) (2) was produced in-house with the appropriate isotype control Abs. All FACS was performed using a BD Biosciences (Mountain View, CA) FACSCalibur and CellQuest, version 4, software.
For intracellular cytokine assays, resident peritoneal M or RAW 264.7 were plated in 24-well plates (5 x 105 cells/well) and, in the case of primary cells, washed 2 h later to remove nonadherent cells. The next day, the M were washed three times with ice-cold medium, and inhibitors were added for 30 min at 4°C (as detailed where appropriate). FITC-labeled zymosan was then added to the wells (20 particles per M) and incubated for 30 min at 37°C to allow binding and internalization to occur. Unbound zymosan was removed by repeated washing at 4°C; medium supplemented with GolgiPlug (BD PharMingen) was added; and the cells were warmed to 37°C for 90 min to allow TNF- production. The cells were washed with ice-cold HBSS, lifted by scraping, and immediately fixed with 1% formaldehyde for 20 min at 4°C. Cells were permeabilized for staining by including 0.5% saponin (Sigma-Aldrich) in all blocking and washing buffers. Intracellular TNF- was detected with allophycocyanin-conjugated anti-TNF- (clone MP6-XT22; BD PharMingen) compared with control Ab (clone A110-1; BD PharMingen). Polymyxin B (Sigma-Aldrich) was included in all TNF- assays (1000 U/ml) to control for endotoxin contamination of commercial mannan preparations.
Statistical analysis
Statistics were calculated using GraphPad Prism (version 2.0; GraphPad Software, San Diego, CA). Repeated measures one-way ANOVA with Tukey’s multiple comparison test was applied where appropriate (*, p < 0.05; **, p < 0.01).
|
Results and Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResults and DiscussionReferences |
|---|
During our previous studies, we identified a mannan-inhibitable component of zymosan recognition on resident peritoneal M (3). To investigate this further, we probed the surface of murine M (both resident and thioglycolate-elicited M) for mannose-binding potential using the synthetic probe Man-PAA-Bio. When these cells were assessed for mannose-binding potential, only the resident peritoneal M (Fig. 1, 
) exhibited significant activity, and it is unlikely to be due to MR, because the expression of the M MR by these cells was poor, as previously reported (3). In addition, thioglycolate-elicited M, which express moderate levels of MR on the surface (3), showed virtually no activity in this assay (Fig. 1, 
). Binding of Man-PAA-Bio to resident peritoneal M was inhibited by mannan, but not the -glucan laminarin, and was cation dependent (Fig. 1), which resembles the classical C-type lectins (22). Interestingly, the binding of the probe was inhibited by both mannose and galactose. Whereas classic Ca2+-dependent lectins like the MR exhibit a significantly higher affinity for mannose than galactose (23, 24), this difference in affinity was found to be less marked for human DC-SIGN and its homolog DC-SIGNR (14). Consequently, we investigated the expression of the murine DC-SIGN homologs by peritoneal M.
|
We assessed the expression of both DC-SIGN and SIGNR1 by RT-PCR on enriched peritoneal M populations (Fig. 2A). Transcripts for DC-SIGN were present in cDNA preparations from both resident and elicited M. The expression of SIGNR1 was more restricted to resident peritoneal cells (Fig. 2A), and because SIGNR1 is known to bind mannose and to be expressed by some M and liver sinusoidal cells (17, 18), we evaluated its expression by FACS using mAb ERTR9 (17, 18). SIGNR1 was evident on the surface of freshly isolated resident peritoneal M, but not on thioglycolate-elicited peritoneal or resident alveolar M (Fig. 2B). To determine whether SIGNR1 was the major receptor responsible for the binding of Man-PAA-Bio to resident peritoneal M, the cells were pretreated with ERTR9, or a control rat IgM, before evaluation of binding activity (Fig. 2C). Pretreatment with ERTR9 prevented binding of the Man-PAA-Bio to resident peritoneal M to the level obtained with mannan, indicating that SIGNR1 was a major receptor mediating this activity (Fig. 2C). This shows that, in cold binding assays, Man-PAA-Bio is a fairly specific probe for the recognition of SIGNR1 activity, even when M MR is also present on the surface of the cell.
|
GR cooperate in the nonopsonic recognition of zymosan by primary cells
We and others (3, 10) have reported that both -glucan and mannan-inhibitable receptors are present on resident peritoneal M. Because we have shown in this study that SIGNR1 is a major MR on resident peritoneal M, we investigated whether SIGNR1 could cooperate with GR in the recognition of zymosan. mAb against GR (2A11) blocked binding of zymosan to a similar degree to that of the soluble -glucan, laminarin (Fig. 2D). Notably, anti-SIGNR1 (ERTR9) blocked the recognition of zymosan in a comparable way to both mannan and EDTA (Fig. 2D). Furthermore, combination of -glucan with mannan, or combination of anti-GR with anti-SIGNR1, largely abrogated the nonopsonic recognition of zymosan by these cells (Fig. 2D). This demonstrates that GR and SIGNR1 are primary nonopsonic pattern recognition receptors on resident peritoneal M that cooperate in an additive way in the recognition of zymosan.
Characterization of SIGNR1 transductants
To verify our findings in primary cells, we next examined this activity in SIGNR1-transduced NIH3T3 fibroblasts, which were confirmed to express SIGNR1 on their surface by FACS (Fig. 3A). Human DC-SIGN has been shown to interact with M. tuberculosis via mannose-capped lipoarabinomannan (25, 26), so to assess our transductants functionally, we measured the binding of FITC-labeled M. tuberculosis. We found that SIGNR1, like human DC-SIGN, exhibited mannan- and EDTA-inhibitable binding to M. tuberculosis (Fig. 3B). We observed that SIGNR1 was capable of mediating zymosan binding to the transduced cells, and that this binding was blocked with mannan but not laminarin (Fig. 3C).
|
C. albicans infection of MR-deficient mice has recently been shown to be relatively normal (27). Furthermore, MR-deficient M exhibited no defect in the phagocytic uptake of C. albicans. We speculated that resident peritoneal M could use SIGNR1 for the nonopsonic recognition of C. albicans in the same way as zymosan (Fig. 3D, left panel). The binding of heat-killed C. albicans by resident peritoneal M was largely inhibited not only by mannan and EDTA but also by the SIGNR1-specific mAb ERTR9. Confirmation that SIGNR1 could interact directly with C. albicans was achieved using NIH3T3-SIGNR1 (Fig. 3D, right panel). This is consistent with the findings of Cambi et al. (28) who have recently reported that human DC-SIGN also binds C. albicans.
Analysis of the phagocytic capacity of SIGNR1
It was recently suggested that human DC-SIGN is a phagocytic receptor capable of mediating the internalization of large particles such as C. albicans (28); however, these studies were conducted using normally phagocytic cells that are likely to express multiple receptors for this yeast. We assessed the ability of murine SIGNR1 to internalize zymosan in the normally nonphagocytic NIH3T3 background. Despite long incubation times at 37°C, NIH3T3-SIGNR1 were found to be only very poorly phagocytic for prebound zymosan particles (Fig. 4), particularly when compared with NIH3T3-GR (Fig. 4 and J. Herre, A. S. J. Marshall, E. Caron, V. L. Tybulewicz, C. Reis-e-Sousa, S. Gordon, and G. D. Brown, manuscript in preparation), indicating that uptake of SIGNR1-ligated particulate material may be facilitated on professional phagocytes by other receptors such as GR.
|
GR, SIGNR1, and TNF- production by M in response to zymosan
We recently demonstrated that, in elicited M, GR cooperates with Toll-like receptor 2 in inducing a proinflammatory response to yeast and zymosan, including the production of TNF-, which could be inhibited with soluble -glucan (8). In resident peritoneal M, however, intracellular TNF- accumulation could be partially inhibited with -glucans (Fig. 5A). This was similar to our previous study of TNF- secreted by resident peritoneal M in response to zymosan, indicating that an alternative GR-independent mechanism for TNF- production existed (29). Furthermore, mannan and the SIGNR1-specific mAb ERTR9 had no significant effect on this activity, supporting the idea that alternative mechanisms were responsible for TNF- production (Fig. 5A and data not shown), suggesting that SIGNR1 was involved in binding but not in the induction of the TNF- response.
|
response to zymosan, we expressed this receptor in RAW 264.7 M, which do not normally express SIGNR1 (data not shown), and compared their responses to zymosan with those of GR-expressing and control RAW 264.7 cells (Fig. 5B and data not shown). As previously reported (8), RAW-FB control cells exhibited minimal zymosan binding and TNF- production, which could be blocked with -glucans, consistent with the low GR expression on these cells. Cells overexpressing GR showed a greatly enhanced -glucan-dependent interaction with zymosan and an increased TNF- response, as expected (8) (data not shown). RAW-SIGNR1 also exhibited an increase in their ability to recognize zymosan (Fig. 5B). The addition of mannan significantly inhibited the binding of zymosan to RAW-SIGNR1 cells but had only marginal, if any, effect on TNF- production. Addition of -glucan had no obvious effect, but combination of -glucan with mannan reduced zymosan binding further, and this resulted in a significant reduction in the amount of TNF- produced. Thus, these data are consistent with SIGNR1 contributing to the nonopsonic recognition of zymosan as observed with primary cells, but not playing a major role in TNF- production, by these cells. Furthermore, these data, and the ability of zymosan to induce enhanced TNF- production in RAW-FB cells when targeted to other surface receptors, such as complement receptor 3 (8), suggests that GR is not essential for the TNF- response to zymosan when an alternative binding/uptake receptor is present, but that it does contribute to the magnitude of this response.
In summary, we show in this study that expression of SIGNR1 by resident peritoneal M results in additive cooperation with GR in the nonopsonic recognition of zymosan (Fig. 2D). We also demonstrate that SIGNR1 is poorly phagocytic, implicating additional receptors on professional phagocytes, such as GR, in the internalization process. Finally, we have shown that uptake of zymosan can occur by either GR or SIGNR1, and this results in TNF- production by M, and although signals generated from the GR are able to induce this response, there is a degree of receptor redundancy in this activity (8). The identification of SIGNR1 as a major MR on resident peritoneal M resolves the mechanism of a long-standing query over the nature of pattern recognition by these cells (9, 10, 11).
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. Philip R. Taylor, Sir William Dunn School of Pathology, Oxford University, South Parks Road, Oxford, OX1 3RE, U.K. E-mail address: ptaylor{at}molbiol.ox.ac.uk
3 Abbreviations used in this paper: GR, -glucan receptor (Dectin-1); M, macrophage; MR, mannose receptor; DC-SIGN, dendritic cell-specific ICAM-3-grabbing nonintegrin; SIGNR1, SIGN-related 1; NIH3T3-SIGNR1, NIH3T3 fibroblast expressing SIGNR1; RAW-SIGNR1, RAW 264.7 M expressing SIGNR1; NIH3T3-GR, NIH3T3 fibroblast expressing GR; Man-PAA-Bio, synthetic biotinylated polymeric mannose probe on a polyacrylamide backbone; MFI, mean fluorescent intensity.
Received for publication August 29, 2003. Accepted for publication October 29, 2003.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResults and DiscussionReferences |
|---|
-glucans. Nature 413:36.[Medline]
-glucan receptor on macrophages. J. Exp. Med. 196:407.-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J. Immunol. 169:3876.-glucan receptor and its alternatively spliced isoforms. J. Biol. Chem. 276:43818.-glucans. J. Exp. Med. 197:1119.-glucan receptors are involved in phagocytosis of unopsonized, heat-killed Saccharomyces cerevisiae by murine macrophages. J. Leukocyte Biol. 54:564.[Abstract]
3)--D-glucan biologic response modifier in two monocyte/macrophage cell lines. J. Immunol. 156:3418.[Abstract]
This article has been cited by other articles:
|
|
 |
|
  S T. Hollmig, K. Ariizumi, and P. D Cruz Jr Recognition of non-self-polysaccharides by C-type lectin receptors dectin-1 and dectin-2 Glycobiology, June 1, 2009; 19(6): 568 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Y. A. Chai, B. J. Kullberg, A. G. Vonk, A. Warris, A. Cambi, J.-P. Latge, L. A. B. Joosten, J. W. M. van der Meer, and M. G. Netea Modulation of Toll-Like Receptor 2 (TLR2) and TLR4 Responses by Aspergillus fumigatus Infect. Immun., May 1, 2009; 77(5): 2184 - 2192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Balestrieri, A. Maekawa, W. Xing, M. H. Gelb, H. R. Katz, and J. P. Arm Group V Secretory Phospholipase A2 Modulates Phagosome Maturation and Regulates the Innate Immune Response against Candida albicans J. Immunol., April 15, 2009; 182(8): 4891 - 4898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Kerrigan, K. M. Dennehy, D. Mourao-Sa, I. Faro-Trindade, J. A. Willment, P. R. Taylor, J. A. Eble, C. Reis e Sousa, and G. D. Brown CLEC-2 Is a Phagocytic Activation Receptor Expressed on Murine Peripheral Blood Neutrophils J. Immunol., April 1, 2009; 182(7): 4150 - 4157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Takagi, M. Numazaki, T. Kajiwara, Y. Abe, M. Ishii, C. Kato, and N. Kojima Cooperation of specific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) and complement receptor type 3 (CR3) in the uptake of oligomannose-coated liposomes by macrophages Glycobiology, March 1, 2009; 19(3): 258 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Saunders, C. M. Walsh, J. L. Barlow, N. E. Mangan, P. R. Taylor, A. N. J. McKenzie, P. Smith, and P. G. Fallon The C-Type Lectin SIGNR1 Binds Schistosoma mansoni Antigens In Vitro, but SIGNR1-Deficient Mice Have Normal Responses during Schistosome Infection Infect. Immun., January 1, 2009; 77(1): 399 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Chaffin Candida albicans Cell Wall Proteins Microbiol. Mol. Biol. Rev., September 1, 2008; 72(3): 495 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rosas, K. Liddiard, M. Kimberg, I. Faro-Trindade, J. U. McDonald, D. L. Williams, G. D. Brown, and P. R. Taylor The Induction of Inflammation by Dectin-1 In Vivo Is Dependent on Myeloid Cell Programming and the Progression of Phagocytosis J. Immunol., September 1, 2008; 181(5): 3549 - 3557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sahly, Y. Keisari, E. Crouch, N. Sharon, and I. Ofek Recognition of Bacterial Surface Polysaccharides by Lectins of the Innate Immune System and Its Contribution to Defense against Infection: the Case of Pulmonary Pathogens Infect. Immun., April 1, 2008; 76(4): 1322 - 1332. [Full Text] [PDF]
|
|
|
|
|
|
A. Koneti, M. J. Linke, E. Brummer, and D. A. Stevens Evasion of Innate Immune Responses: Evidence for Mannose Binding Lectin Inhibition of Tumor Necrosis Factor Alpha Production by Macrophages in Response to Blastomyces dermatitidis Infect. Immun., March 1, 2008; 76(3): 994 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Rothfuchs, A. Bafica, C. G. Feng, J. G. Egen, D. L. Williams, G. D. Brown, and A. Sher Dectin-1 Interaction with Mycobacterium tuberculosis Leads to Enhanced IL-12p40 Production by Splenic Dendritic Cells J. Immunol., September 15, 2007; 179(6): 3463 - 3471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Doz, S. Rose, J. Nigou, M. Gilleron, G. Puzo, F. Erard, B. Ryffel, and V. F. J. Quesniaux Acylation Determines the Toll-like receptor (TLR)-dependent Positive Versus TLR2-, Mannose Receptor-, and SIGNR1-independent Negative Regulation of Pro-inflammatory Cytokines by Mycobacterial Lipomannan J. Biol. Chem., September 7, 2007; 282(36): 26014 - 26025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Jouault, M. El Abed-El Behi, M. Martinez-Esparza, L. Breuilh, P.-A. Trinel, M. Chamaillard, F. Trottein, and D. Poulain Specific Recognition of Candida albicans by Macrophages Requires Galectin-3 to Discriminate Saccharomyces cerevisiae and Needs Association with TLR2 for Signaling J. Immunol., October 1, 2006; 177(7): 4679 - 4687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. McGreal, M. Rosas, G. D. Brown, S. Zamze, S. Y.C. Wong, S. Gordon, L. Martinez-Pomares, and P. R. Taylor The carbohydrate-recognition domain of Dectin-2 is a C-type lectin with specificity for high mannose Glycobiology, May 1, 2006; 16(5): 422 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. M. Heinsbroek, P. R. Taylor, M. Rosas, J. A. Willment, D. L. Williams, S. Gordon, and G. D. Brown Expression of Functionally Different Dectin-1 Isoforms by Murine Macrophages J. Immunol., May 1, 2006; 176(9): 5513 - 5518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Suram, G. D. Brown, M. Ghosh, S. Gordon, R. Loper, P. R. Taylor, S. Akira, S. Uematsu, D. L. Williams, and C. C. Leslie Regulation of Cytosolic Phospholipase A2 Activation and Cyclooxygenase 2 Expression in Macrophages by the beta-Glucan Receptor J. Biol. Chem., March 3, 2006; 281(9): 5506 - 5514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nagaoka, K. Takahara, K. Tanaka, H. Yoshida, R. M. Steinman, S.-i. Saitoh, S. Akashi-Takamura, K. Miyake, Y. S. Kang, C. G. Park, et al. Association of SIGNR1 with TLR4-MD-2 enhances signal transduction by recognition of LPS in gram-negative bacteria Int. Immunol., July 1, 2005; 17(7): 827 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Fernandez, S. Alonso, I. Valera, A. G. Vigo, M. Renedo, L. Barbolla, and M. S. Crespo Mannose-Containing Molecular Patterns Are Strong Inducers of Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Macrophages J. Immunol., June 15, 2005; 174(12): 8154 - 8162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. de la Rosa, M. Yanez-Mo, R. Samaneigo, D. Serrano-Gomez, L. Martinez-Munoz, E. Fernandez-Ruiz, N. Longo, F. Sanchez-Madrid, A. L. Corbi, and P. Sanchez-Mateos Regulated recruitment of DC-SIGN to cell-cell contact regions during zymosan-induced human dendritic cell aggregation J. Leukoc. Biol., May 1, 2005; 77(5): 699 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Herre, A. S. J. Marshall, E. Caron, A. D. Edwards, D. L. Williams, E. Schweighoffer, V. Tybulewicz, C. R. e Sousa, S. Gordon, and G. D. Brown Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages Blood, December 15, 2004; 104(13): 4038 - 4045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lanoue, M. R. Clatworthy, P. Smith, S. Green, M. J. Townsend, H. E. Jolin, K. G.C. Smith, P. G. Fallon, and A. N.J. McKenzie SIGN-R1 Contributes to Protection against Lethal Pneumococcal Infection in Mice J. Exp. Med., December 6, 2004; 200(11): 1383 - 1393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Hobson, C. A. Munro, S. Bates, D. M. MacCallum, J. E. Cutler, S. E. M. Heinsbroek, G. D. Brown, F. C. Odds, and N. A.R. Gow Loss of Cell Wall Mannosylphosphate in Candida albicans Does Not Influence Macrophage Recognition J. Biol. Chem., September 17, 2004; 279(38): 39628 - 39635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takahara, Y. Yashima, Y. Omatsu, H. Yoshida, Y. Kimura, Y.-S. Kang, R. M. Steinman, C. G. Park, and K. Inaba Functional comparison of the mouse DC-SIGN, SIGNR1, SIGNR3 and Langerin, C-type lectins Int. Immunol., June 1, 2004; 16(6): 819 - 829. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
MFI (MFI with TNF-