Phagocytosis and Phagosome Maturation Are Regulated by Calcium in J774 Macrophages Interacting with Unopsonized Prey

Tejle, Katarina; Magnusson, Karl‐Eric; Rasmusson, Birgitta

doi:10.1023/a:1022025903688

Cited by 35 publications

(25 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in striking contrast to other yeasts: unopsonized Saccharomyces cerevisiae or Candida albicans are phagocytosed after less than an hour of co-incubation (Lohse and Johnson, 2008; Tejle et al, 2002). Opsonizing agents are likely present in lower levels early in infection.…”

Section: Introductioncontrasting

confidence: 57%

A Major Role for Capsule-Independent Phagocytosis-Inhibitory Mechanisms in Mammalian Infection by Cryptococcus neoformans

Chun

Brown

Madhani

2011

Cell Host & Microbe

104

View full text Add to dashboard Cite

Summary The anti-phagocytic polysaccharide capsule of the human fungal pathogen Cryptococcus neoformans is a major virulence attribute. However, previous studies of the pleiotropic virulence determinant Gat201, a GATA-family transcription factor, suggested that capsule-independent antiphagocytic mechanisms exist. We have determined that Gat201 controls the mRNA levels of ~1100 genes (16% of the genome) and binds the upstream regions of ~130 genes. Seven Gat201-bound genes encode for putative and known transcription factors—including two previously implicated in virulence—suggesting an extensive regulatory network. Systematic analysis pinpointed two critical Gat201-bound genes, GAT204 (a transcription factor) and BLP1, which account for much of the capsule-independent antiphagocytic function of Gat201. A strong correlation was observed between the quantitative effects of single and double mutants on phagocytosis in vitro and on host colonization in vivo. This genetic dissection provides evidence that capsule-independent anti-phagocytic mechanisms are pivotal for successful mammalian infection by C. neoformans.

show abstract

Section: Introductioncontrasting

confidence: 57%

A Major Role for Capsule-Independent Phagocytosis-Inhibitory Mechanisms in Mammalian Infection by Cryptococcus neoformans

Chun

Brown

Madhani

2011

Cell Host & Microbe

104

View full text Add to dashboard Cite

show abstract

“…Calcium (Ca 2+ ) was shown to play a role in phagocytosis in mammalian cells, but its precise role in this process remains unclear and somewhat controversial. A rise in intracellular Ca 2+ concentration ([Ca 2+ ]i) in mammalian phagocytes was previously described during phagocytosis of various particles, but the molecular mechanisms underlying this rise in [Ca 2+ ]i are poorly understood [46], [47], [48]. Thus our results on PKD2 provide us with a new component of the molecular machinery underlying Ca 2+ homeostasis in phagocytosis.…”

Section: Discussionsupporting

confidence: 55%

The Drosophila TRPP Cation Channel, PKD2 and Dmel/Ced-12 Act in Genetically Distinct Pathways during Apoptotic Cell Clearance

et al. 2012

View full text Add to dashboard Cite

Apoptosis, a genetically programmed cell death, allows for homeostasis and tissue remodelling during development of all multi-cellular organisms. Phagocytes swiftly recognize, engulf and digest apoptotic cells. Yet, to date the molecular mechanisms underlying this phagocytic process are still poorly understood. To delineate the molecular mechanisms of apoptotic cell clearance in Drosophila, we have carried out a deficiency screen and have identified three overlapping phagocytosis-defective mutants, which all delete the fly homologue of the ced-12 gene, known as Dmel\ced12. As anticipated, we have found that Dmel\ced-12 is required for apoptotic cell clearance, as for its C. elegans and mammalian homologues, ced-12 and elmo, respectively. However, the loss of Dmel\ced-12 did not solely account for the phenotypes of all three deficiencies, as zygotic mutations and germ line clones of Dmel\ced-12 exhibited weaker phenotypes. Using a nearby genetically interacting deficiency, we have found that the polycystic kidney disease 2 gene, pkd2, which encodes a member of the TRPP channel family, is also required for phagocytosis of apoptotic cells, thereby demonstrating a novel role for PKD2 in this process. We have also observed genetic interactions between pkd2, simu, drpr, rya-r44F, and retinophilin (rtp), also known as undertaker (uta), a gene encoding a MORN-repeat containing molecule, which we have recently found to be implicated in calcium homeostasis during phagocytosis. However, we have not found any genetic interaction between Dmel\ced-12 and simu. Based on these genetic interactions and recent reports demonstrating a role for the mammalian pkd-2 gene product in ER calcium release during store-operated calcium entry, we propose that PKD2 functions in the DRPR/RTP pathway to regulate calcium homeostasis during this process. Similarly to its C. elegans homologue, Dmel\Ced-12 appears to function in a genetically distinct pathway.

show abstract

“…This is in striking contrast to other yeast such as Sacchromyces cerevisiae or Candida albicans , or inert objects such as latex beads, all of which are taken up after less than an hour of co-incubation [7], [8], [9]. These studies suggest the possibility that C. neoformans may inhibit or evade unopsonized phagocytosis by macrophages.…”

Section: Introductionmentioning

confidence: 80%

Ctr2 Links Copper Homeostasis to Polysaccharide Capsule Formation and Phagocytosis Inhibition in the Human Fungal Pathogen Cryptococcus neoformans

Chun

Madhani

2010

PLoS ONE

View full text Add to dashboard Cite

Cryptococcus neoformans is a human opportunistic fungal pathogen responsible for ∼1/3 of HIV/AIDS deaths worldwide. This budding yeast expresses a polysaccharide capsule necessary for virulence. Capsule production inhibits phagocytosis by macrophages. Here we describe results that link copper homeostasis to capsule production and the inhibition of phagocytosis. Specifically, using Agrobacterium-mediated insertional mutagenesis, we identified an insertion in the promoter region of the putative copper transporter-encoding gene CTR2 that results in reduced expression of CTR2 and increased phagocytosis by murine RAW264.7 macrophages. The mutant also displayed sensitivity to copper starvation and defects in polysaccharide capsule production and melanization. These defects were all reversed by genetic correction of the promoter insertion by homologous targeting. Several melanization-defective mutants identified previously, those in the RIM20, RIM101, and VPS25 genes, also display sensitivity to copper starvation, reduced capsule production and increased phagocytosis. Together these results indicate a previously undescribed link between copper homeostasis to polysaccharide capsule production and phagocytosis inhibition in Cryptococcus neoformans.

show abstract

Phagocytosis and Phagosome Maturation Are Regulated by Calcium in J774 Macrophages Interacting with Unopsonized Prey

Cited by 35 publications

References 33 publications

A Major Role for Capsule-Independent Phagocytosis-Inhibitory Mechanisms in Mammalian Infection by Cryptococcus neoformans

A Major Role for Capsule-Independent Phagocytosis-Inhibitory Mechanisms in Mammalian Infection by Cryptococcus neoformans

The Drosophila TRPP Cation Channel, PKD2 and Dmel/Ced-12 Act in Genetically Distinct Pathways during Apoptotic Cell Clearance

Ctr2 Links Copper Homeostasis to Polysaccharide Capsule Formation and Phagocytosis Inhibition in the Human Fungal Pathogen Cryptococcus neoformans

Contact Info

Product

Resources

About