Role of the Mannose Receptor in the Immune Response

Apostolopoulos, Vasso; McKenzie, Ifc

doi:10.2174/1566524013363645

Cited by 145 publications

(119 citation statements)

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“…Thus, it is likely that the locally produced M-CSF and IL-10 promote homeostatic Mf with the ability of clearing infections without compromising fetal tolerance. In this study, CD206 and CD209 seem to be important receptors with main functions to recognize, process, and clear potentially harmful pathogens (54,55). Interestingly, it was recently shown that the scavenger receptor CD163, being expressed in tissue resident Mf and involved in tissue homeostasis (56), also mediated the recognition and binding of bacteria by Mf (57).…”

Section: Discussionmentioning

confidence: 70%

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Svensson

Jenmalm

Matussek

et al. 2011

The Journal of Immunology

309

314

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During pregnancy, the maternal immune system is challenged by the presence of the fetus, which must be tolerated despite being semiallogeneic. Uterine mucosal (or decidual) macrophages (Mϕ), one of the major leukocyte populations at the fetal–maternal interface, have been implicated in fetal tolerance, but information regarding their regulation is scarce. In this study, we investigated the role of several factors potentially involved in the differentiation and polarization of decidual Mϕ with an in vitro Mϕ differentiation model. By using flow cytometry, we showed that M-CSF and IL-10 were potent inducers of M2 (immunoregulatory) Mϕ markers expressed on human decidual Mϕ (CD14, CD163, CD206, CD209). In contrast, proinflammatory stimuli, and unexpectedly also the Th2-associated IL-4 and IL-13, induced different patterns of expression, indicating that a Th2-dominated environment is not required for decidual Mϕ polarization. M-CSF/IL-10–stimulated and decidual Mϕ also showed similar cytokine secretion patterns, with production of IL-10 as well as IL-6, TNF, and CCL4. Conversely, the proinflammatory, LPS/IFN-γ–stimulated Mϕ produced significantly higher levels of TNF and no IL-10. We also used a gene array with 420 Mϕ-related genes, of which 100 were previously reported to be regulated in a global gene expression profiling of decidual Mϕ, confirming that M-CSF/IL-10–induced Mϕ are closely related to decidual Mϕ. Taken together, our results consistently point to a central role for M-CSF and in particular IL-10 in the shaping of decidual Mϕ with regulatory properties. These cytokines may therefore play an important role in supporting the homeostatic and tolerant immune milieu required for a successful pregnancy.

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Section: Discussionmentioning

confidence: 70%

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Svensson

Jenmalm

Matussek

et al. 2011

The Journal of Immunology

309

314

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“…4C). Thus, mannan conjugation enhanced Th2-polarized anti-Aβ antibody responses, as has been observed after conjugation of mannan with other peptide immunogens (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,1996Vaughan et al, 1999;Apostolopoulos and McKenzie, 2001). …”

Section: Mannosylated Aβ 28 Induced a Th2 Polarized Immune Responsementioning

confidence: 62%

“…Mannan has previously been shown to be a potent molecular adjuvant enhancing both B-and T-cell immune responses, as well as antigen uptake and presentation (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,2000Engering et al, 1997aEngering et al, ,1997bKaranikas et al, 1997;Gröger et al, 2000;Linehan et al, 2000;Vaughan et al, 2000;Stambas et al, 2002aStambas et al, ,2002bStambas et al, ,2005. This molecular adjuvant not only enhanced antibody responses specific to appropriate peptide attached to it (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,2000, but under certain conditions also induced Th2-polarized immunity (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,1996Vaughan et al, 1999;Apostolopoulos and McKenzie, 2001). Taking advantage of this property of mannan, we designed a novel AD vaccine that will induce Th2-prone immune responses directed to the Aβ peptide.…”

Section: Discussionmentioning

confidence: 98%

“…Enhancement of immune responses against several mannosylated antigens, including peptide antigens, has been demonstrated (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,2000. Under certain conditions, mannosylated antigens induced strong Th2 type anti-inflammatory responses with high levels of IgG1 antibodies, IL4 and IL10 production (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,1996Vaughan et al, 1999;Apostolopoulos and McKenzie, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Aβ-Immunotherapy for Alzheimer's Disease Using Mannan–Amyloid-Beta Peptide Immunoconjugates

Ghochikyan

Petrushina

Lees³

et al. 2006

DNA and Cell Biology

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In Alzheimer's disease (AD) the accumulation of pathological forms of the beta-amyloid (Aβ) peptide are believed to be causal factors in the neurodegeneration that results in the loss of cognitive function in patients. Anti-Aβ antibodies have been shown to reduce Aβ levels in transgenic mouse models of AD and in AN-1792 clinical trial on AD patients; however, the clinical trial was halted when some patients developed meningoencephalitis. Theories on the cause of the adverse events include proinflammatory "primed patients," a Th1-inducing adjuvant, and Aβ autoreactive T cells. New immunotherapy approaches are being developed to eliminate these putative risk factors. Mannan, which is recognized by pattern recognition receptors of the innate immune system, can be utilized as a molecular adjuvant to promote a Th2-mediated immune response to conjugated B cell epitopes. The N-terminus of Aβ was conjugated to mannan, and used to immunize mice with low concentrations of immunoconjugate, without a conventional adjuvant. Mannan induced a significant and highly polarized toward Th2 phenotype anti-Aβ antibody response not only in BALB/c, but also in B6SJL F1 mice. New preclinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse immune response that occurred in the first clinical trial.

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“…It has been suggested that GP64 interacts with the mannose receptor, which is expressed principally on macrophages and DCs. Mannose receptor is involved in endocytosis/phagocytosis and plays an important role in host defenses and the induction of innate immunity (42). However, there are several lines of evidence to suggest that GP64 is not the principal actor in the stimulatory properties of BVs.…”

Section: Discussionmentioning

confidence: 99%

Insect Baculoviruses Strongly Potentiate Adaptive Immune Responses by Inducing Type I IFN

Hervás-Stubbs

Rueda

López

et al. 2007

The Journal of Immunology

155

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Baculoviruses (BVs) are dsDNA viruses that are pathogenic for insects. They have been used worldwide as selective bioinsecticides and for producing recombinant proteins in insect cells. Surprisingly, despite their widespread use in research and industry and their dissemination in the environment, the potential effects of these insect viruses on the immune responses of mammals remain totally unknown. We show in this study that BVs have strong adjuvant properties in mice, promoting potent humoral and CD8+ T cell adaptive responses against coadministered Ag. BVs also induce the in vivo maturation of dendritic cells and the production of inflammatory cytokines. We demonstrate that BVs play a major role in the strong immunogenicity of virus-like particles produced in the BV-insect cell expression system. The presence of even small numbers of BVs among the recombinant proteins produced in the BV expression system may therefore strengthen the immunological properties of these proteins. This adjuvant behavior of BVs is mediated primarily by IFN-αβ, although mechanisms independent of type I IFN signaling are also involved. This study demonstrates that nonpathogenic insect viruses may have a strong effect on the mammalian immune system.

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Role of the Mannose Receptor in the Immune Response

Cited by 145 publications

References 0 publications

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Aβ-Immunotherapy for Alzheimer's Disease Using Mannan–Amyloid-Beta Peptide Immunoconjugates

Insect Baculoviruses Strongly Potentiate Adaptive Immune Responses by Inducing Type I IFN

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