Mechanisms of Phagocytosis in Macrophages

Aderem, Alan; Underhill, David

doi:10.1146/annurev.immunol.17.1.593

Cited by 2,369 publications

(1,913 citation statements)

References 148 publications

Supporting

Mentioning

1,839

Contrasting

Unclassified

Order By: Relevance

“…Circulating monocytes and tissue macrophages (Mu) mediate much of this innate immune response [1]. The strategy of recognition in the innate response is mediated by the coordinated action of pathogen-associated molecular patterns and pattern recognition receptors.…”

Section: Introductionmentioning

confidence: 99%

IL‐13 induces expression of CD36 in human monocytes through PPARγ activation

et al. 2007

View full text Add to dashboard Cite

The class B scavenger receptor CD36 is a component of the pattern recognition receptors on monocytes that recognizes a variety of molecules. CD36 expression in monocytes depends on exposure to soluble mediators. We demonstrate here that CD36 expression is induced in human monocytes following exposure to IL-13, a Th2 cytokine, via the peroxisome proliferator-activated receptor (PPAR)c pathway. Induction of CD36 protein was paralleled by an increase in CD36 mRNA. The PPARc pathway was demonstrated using transfection of a PPARc expression plasmid into the murine macrophage cell line RAW264.7, expressing very low levels of PPARc, and in peritoneal macrophages from PPARc-conditional null mice. We also show that CD36 induction by IL-13 via PPARc is dependent on phospholipase A2 activation and that IL-13 induces the production of endogenous 15-deoxy-D 12,14 -prostaglandin J 2 , an endogenous PPARc ligand, and its nuclear localization in human monocytes. Finally, we demonstrate that CD36 and PPARc are involved in IL-13-mediated phagocytosis of Plasmodium falciparum-parasitized erythrocytes. These results reveal a novel role for PPARc in the alternative activation of monocytes by IL-13, suggesting that endogenous PPARc ligands, produced by phospholipase A2 activation, could contribute to the biochemical and cellular functions of CD36.Leukocyte signaling * These 2 authors contributed equally to this work. IntroductionThe innate immune system protects the host in the early phase of infection. Circulating monocytes and tissue macrophages (Mu) mediate much of this innate immune response [1]. The strategy of recognition in the innate response is mediated by the coordinated action of pathogen-associated molecular patterns and pattern recognition receptors. Scavenger receptors and mannose receptor are important pattern recognition receptors in monocytes/Mu [2,3]. The modulation of the expression of these receptors may be critical in the role of these cells in antigen processing, scavenging, and host defence against pathogens. Several members of the scavenger receptor family, including Mu class A scavenger receptors and CD36, have been identified as receptors for modified lipoproteins on Mu, and their relevance to lipid uptake has been demonstrated in vitro and in vivo [4]. The scavenger receptor CD36, an 88-kDa integral membrane protein, is a class B scavenger receptor expressed on a wide variety of cells, in particular on monocytes and monocytederived Mu [5,6]. CD36 is known as a receptor for the uptake of oxidatively modified low-density lipoprotein (LDL) [7] and is also able to bind anionic phospholipid phosphatidylserine [8]. This scavenger receptor is implicated in the clearance of apoptotic cells [9]. Recently, McGilvray and colleagues [10] described a CD36-dependent nonopsonic phagocytosis of erythrocytes containing P. falciparum, by monocytes and culture-derived Mu, and a decrease in the parasiteinduced TNF secretion by monocytes/Mu. These processes were accentuated by CD36 up-regulation by peroxisome proliferator-acti...

show abstract

Section: Introductionmentioning

confidence: 99%

IL‐13 induces expression of CD36 in human monocytes through PPARγ activation

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The gram-negative bacterial cell wall component lipopolysaccharide (LPS) is an endotoxin that triggers a myriad of immunoregulatory cytokines that participate in eliminating the bacterial insult [1]. LPS associates with a 60-kD serum protein called lipidbinding protein and this complex subsequently associates with CD14, a 50-kD glycoprotein surface receptor constitutively expressed primarily by macrophages and monocytes, two cellular components of the innate immune system [2,3].…”

Section: Introductionmentioning

confidence: 99%

STAT‐1‐mediated repression of monocyte interleukin‐10 gene expression in vivo

et al. 2006

View full text Add to dashboard Cite

There have been substantial advances in understanding the events that regulate gene expression at the cellular and molecular level; however, there has been limited progress integrating this information to understand how biological systems function in vivo. For example, the anti‐inflammatory cytokine IL‐10 is thought to down‐regulate the effects of the pro‐inflammatory cytokine IFN‐γ on monocyte activation following LPS stimulation. However, the often‐postulated reciprocal regulation of IL‐10 gene expression by IFN‐γ has not been studied in vivo. Here we demonstrate that the regulation of IL‐10 gene expression has at least two phases following challenge with LPS or a gram‐negative organism. In C57BL/6 mice, early IL‐10 induction occurs independently of STAT‐1, while a delayed active repression of IL‐10 gene expression is critically dependent on STAT‐1, but only partially dependent upon IFN‐α/β and IFN‐γ. This in vivo IL‐10 production comes from blood monocytes, but not tissue macrophages, and cannot be reproduced in vitro. This study provides new insights into the regulation of IL‐10 following challenge with a gram‐negative organism, and highlights the importance of studying these cytokine regulatory pathways in vivo.

show abstract

“…The effect of the phagocyte receptor involved in mediating differences in internalization mechanisms is illustrated also by the mannose receptor (MR), which recognizes mannose and fucose on bacterial surfaces. Unlike FcR and CR-mediated phagocytosis, MRmediated phagocytosis is not associated with accumulation of the cytoskeletal proteins vinculin and paxillin around the phagosomes [1].…”

Section: Cell Biologymentioning

confidence: 90%

“…Whereas in antibody (FcR)-mediated phagocytosis, pseudopodia tightly engulf opsonized bacteria before drawing them into the macrophage, in CR-mediated phagocytosis, opsonized bacteria sink into the macrophage without marked pseudopodia [1]. FcRinduced phagocytosis is strongly associated with production of reactive oxygen intermediates (oxidative burst) and pro-inflammatory mediators, whereas CR-mediated phagocytosis does not induce this effect [1]. The effect of the phagocyte receptor involved in mediating differences in internalization mechanisms is illustrated also by the mannose receptor (MR), which recognizes mannose and fucose on bacterial surfaces.…”

Section: Cell Biologymentioning

confidence: 99%

Rhodococcus equi

2004

View full text Add to dashboard Cite

-Rhodococcus equi is an important cause of subacute or chronic abscessating bronchopneumonia of foals up to 3-5 months of age. It shares the lipid-rich cell wall envelope characteristic of the mycolata, including Mycobacterium tuberculosis, as well as the ability of pathogenic members of this group to survive within macrophages. The possession of a large virulence plasmid in isolates recovered from pneumonic foals is crucial for virulence. The plasmid contains an 27 kb pathogenicity island (PI) that encodes seven related virulence-associated proteins (Vaps), including the immunodominant surface-expressed protein, VapA. Only PI genes are differentially expressed when the organism is grown in macrophages in vitro. Ten of the PI genes, including six Vap genes, have signal sequences, suggesting that they are exported from the cell to interact with the macrophage. Different PI genes are regulated by temperature, pH, iron, oxidative stress and probably also by magnesium, all environmental changes encountered after environmental R. equi are inhaled in dust and are ingested into macrophages in the lung. The basis of pathogenicity of R. equi is its ability to multiply in and eventually to destroy alveolar macrophages. Infectivity is largely or exclusively limited to cells of the monocyte-macrophage lineage. Current evidence suggests that infection of foals with virulent R. equi results in some foals in subversion of cellmediated immunity and development of an ineffective and sometimes lethal Th2-based immune response. Significant progress has been made recently in the development of R. equi-E. coli shuttle vectors, transformation and random and site specific mutagenesis procedures, all of which will be important in molecular dissection of the mechanisms by which R. equi subverts normal macrophage killing mechanisms and cell-mediated immunity.

show abstract

Mechanisms of Phagocytosis in Macrophages

Cited by 2,369 publications

References 148 publications

IL‐13 induces expression of CD36 in human monocytes through PPARγ activation

IL‐13 induces expression of CD36 in human monocytes through PPARγ activation

STAT‐1‐mediated repression of monocyte interleukin‐10 gene expression in vivo

Rhodococcus equi

Contact Info

Product

Resources

About