Analysis of innate defences against Plasmodium falciparum in immunodeficient mice

Arnold, Ludovic; Tyagi, Rajeev K.; Mejia, Pedro; Rooijen, Nico van; Pérignon, Jean‐Louis; Druilhe, Pierre

doi:10.1186/1475-2875-9-197

Cited by 28 publications

(46 citation statements)

References 50 publications

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“…To address this idea directly, we depleted granulocytes from both strains by administering anti-Ly6-G antibodies, which have previously been shown to selectively deplete granulocytes in vivo (36). Flow analysis confirmed that after antibody depletion, granulocyte numbers were reduced to below detection levels in both strains (Supplemental Figure 4).…”

Section: Figurementioning

confidence: 81%

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Jones¹,

Roberts²,

Robbins³

et al. 2013

J. Clin. Invest.

177

164

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Extended circulation of nanoparticles in blood is essential for most clinical applications. Nanoparticles are rapidly cleared by cells of the mononuclear phagocyte system (MPS). Approaches such as grafting polyethylene glycol onto particles (PEGylation) extend circulation times; however, these particles are still cleared, and the processes involved in this clearance remain poorly understood. Here, we present an intravital microscopybased assay for the quantification of nanoparticle clearance, allowing us to determine the effect of mouse strain and immune system function on particle clearance. We demonstrate that mouse strains that are prone to Th1 immune responses clear nanoparticles at a slower rate than Th2-prone mice. Using depletion strategies, we show that both granulocytes and macrophages participate in the enhanced clearance observed in Th2-prone mice. Macrophages isolated from Th1 strains took up fewer particles in vitro than macrophages from Th2 strains. Treating macrophages from Th1 strains with cytokines to differentiate them into M2 macrophages increased the amount of particle uptake. Conversely, treating macrophages from Th2 strains with cytokines to differentiate them into M1 macrophages decreased their particle uptake. Moreover, these results were confirmed in human monocyte-derived macrophages, suggesting that global immune regulation has a significant impact on nanoparticle clearance in humans. IntroductionThe potential clinical applications of nanoparticles and nanoformulations have been investigated for more than 30 years. Nanoparticle approaches have the potential to revolutionize drug delivery by allowing for the encapsulation of drugs with poor solubility or stability in a stable carrier particle. In addition, targeting nanoparticles to specific pathological sites may allow an increased effective dose of drug at the needed site, while decreasing systemic drug exposure, and therefore side effects. However, to date, only 2 nanoformulations for cancer treatment have been approved for clinical use (liposomal doxorubicin [Doxil] and protein-bound paclitaxel [Abraxane]) (1-3). One major obstacle for the use of nanoparticles in vivo is rapid clearance by the cells of the reticuloendothelial system (RES)/mononuclear phagocyte system (MPS) (4-7). In addition to rapid clearance, variable activity of the MPS among patients leads to widely variable pharmacokinetics of nanoformulations in the clinic, reducing the efficacy of both approved and future experimental nanoformulations (8).

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Section: Figurementioning

confidence: 81%

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Jones¹,

Roberts²,

Robbins³

et al. 2013

J. Clin. Invest.

177

164

View full text Add to dashboard Cite

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“…Additionally, NSG mice shown lesser effect of aging which was due to the minimalized effect by interposition impact rendered by the IL-2Rγ mutation, along with a small sample size exhibiting marginal benefit of aging in the said mouse strain. The NSG-IV murine model when transplanted with human cells showed a great complementation of IL-2Rγ mutation byclo-lip treatment in controlling inflammation mounted by the cell engraftment which reportedly showed the reduction in the erythrophagocytosis [1,2,[4][5][6][7].…”

Section: Mutation In (Il-2r) γ-Chainmentioning

confidence: 99%

“…which is highly evolved and a complex organism. The mercurial behavior of parasite because of the secretion of tens of thousands of proteins [4,5,48]. A) Upper panel shows significant human blood chimerism in NSG mice over the period of more than 21 days, and B) lower panel illustrates the sizeable parasitemia using three (PAM, 3D7 and K1) P. falciparum strains in the huRBC reconstituted NSG mice.…”

Section: The Malaria Vaccine Development: a Challenging Taskmentioning

confidence: 99%

“…The clo-lip (clodronate-loaded liposome) is scavenged by the cells of monocyte-macrophage lineage, triggering their apoptosis and creating stroma for huHep grafting. Recent surge in the usage of humanized mouse models owing to the results from earlier findings [4,5] in which clodronate-loaded liposome treatment depletes the macrophage level in an immunodeficient mouse (Pf-NSG-IV) to study of asexual blood stage infection of P. falciparum (Figures 2 and 3).…”

mentioning

confidence: 99%

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Liposome-Mediated Immunosuppression Plays an Instrumental Role in the Development of “Humanized Mouse” to Study Plasmodium falciparum

Agrawal¹,

Vyas²,

Hafeji³

et al. 2017

Liposomes

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The material world has been getting prone toward infectious diseases, and therefore novel strategies should be devised to treat chronic infectious disorders. The translational biomedical research scientists made early attempts to develop mouse-human chimera (humanized mouse) through the reconstitution of immunodeficient mouse with engraftment of human cells and tissues. Although the humanized mouse proved to be an effective tool in understanding various diseases such as human malaria and hepatitis, however, drug administration, retention capacity of the administered drug, toxicity, and ethical constraints are some of the major issues and need to be objectively addressed. The "humanization" of immunodeficient mouse needs pharmacological immunomodulatory reagents to control the excessively recruited cells of monocytemacrophage lineage. Therefore, administration of liposome loaded with hydrophobic drug (clodronate) to induce selective apoptosis through "suicidal approach" in myeloid cells plays an instrumental role for controlling residual nonadaptive immune response of the host. Liposomes are spherical and hollow-structures consisting of lipid bilayer-and are used for the delivery of drug and vaccine candidates. The surfaceengineered liposomes (ligand anchored) are used for targeted and controlled delivery. Clodronate-loaded liposomes play a pivotal role in developing humanized mouse. This mouse holds relevance to study pathophysiology and immunopathology of human malaria parasite, P. falciparum. The liposomal delivery of clodronate administered in immunodeficient mice to modulate their innate immune system is an amenable strategy with the minimal/acceptable range of systemic toxicity.

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“…The resulting new IV model based on NSG mice presents several advantages over previously available models. It offers greater reproducibility, with 100% of mice successfully grafted without the need for mouse-adapted parasites, consistent curves of parasitemia, and high levels of infection with up to 40-50% of total erythrocytes infected (Arnold et al, 2010).…”

mentioning

confidence: 99%