**7. Conclusion**

In conclusion, the chapter demonstrates that the careful selection of mice with combined deficiencies of adaptive and innate immunity, and the better control of innate immune defenses by improving immunomodulatory protocols and using anti-inflammatory substances, could provide a reproducible, long lasting and straightforward mouse model of

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## **8. Abbreviations**

NOD- Non-Obese Diabetic; SCID-Severe Combined Immunodeficiency; IL2Rγ- Interleukin-2 Receptor γ-chain; NK- Natural Killer; PBMCs: Peripheral Blood Monocytes; HSCs: Hematopoietic stem cells; *Rag-*Recombination-Activating Gene; IL-Interleukin; huRBCs— Human Red Blood Cells; PMN-Polymorphonuclear; SAGM- Adenine, Glucose and Mannitol solution; CL2MDP- Dichloro-Methylene-Diphosphonate; NSG-NOD scid gamma; TGF-Tumor Growth Factor; APC-Antigen Presenting Cell; FACS- Fluorescence Activated Cell sorting; FCS- Fetal Calf Serum; FITC- Fluorescein isothiocyanate, phorbol-12-myristate-13-acetate (PMA)

#### **9. References**


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NOD- Non-Obese Diabetic; SCID-Severe Combined Immunodeficiency; IL2Rγ- Interleukin-2 Receptor γ-chain; NK- Natural Killer; PBMCs: Peripheral Blood Monocytes; HSCs: Hematopoietic stem cells; *Rag-*Recombination-Activating Gene; IL-Interleukin; huRBCs— Human Red Blood Cells; PMN-Polymorphonuclear; SAGM- Adenine, Glucose and Mannitol solution; CL2MDP- Dichloro-Methylene-Diphosphonate; NSG-NOD scid gamma; TGF-Tumor Growth Factor; APC-Antigen Presenting Cell; FACS- Fluorescence Activated Cell sorting; FCS- Fetal Calf Serum; FITC- Fluorescein isothiocyanate, phorbol-12-myristate-

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**7** 

*1France 2Singapore* 

**Human Erythrocyte Remodelling** 

Xue Yan Yam1,2, Alassane Mbengue1 and Catherine Braun-Breton1

Making the erythrocyte its home for 48 hours has important consequences for the human malaria parasite *Plasmodium falciparum*. Indeed, erythrocytes are terminally differentiated cells that lack a nucleus as well as intracellular organelles, are thus unable to endocytose or exocytose macromolecules, and have lost several membrane transport activities upon differentiation. Consequently, the parasite has to deeply remodel its host cell, from the very beginning to ensure its entry into the red blood cell, throughout its growth and multiplication to fulfil its needs for extracellular nutrients, and to the very end of its intraerythrocytic development with the parasite-induced opening and curling of the red cell membrane leading to the dispersion of newly formed merozoites into the blood flow. The most spectacular, and first reported, modifications of the red blood cell membrane induced by *P. falciparum* are electron dense protrusions named knobs and consisting of parasite proteins exported to the red cell membrane and sub-membrane skeleton where they eventually interact with host cell proteins. Knobs are directly related to the severity of *falciparum* malaria because they mediate adherence of infected erythrocytes to the microvasculature endothelium. More recent studies have revealed that the parasite might export several hundreds of proteins, as well as membrane compartments, to the red cell and divert enzymatic and structural host proteins to make the erythrocyte a suitable environment for its growth. In the last decade, remodelling of its host cell by *Plasmodium falciparum* has become an important and growing field of research. In this review, we will describe the current stage of knowledge concerning red blood cell remodelling by *Plasmodium falciparum* and the role of these parasite-induced modifications for its growth

Apicomplexan parasites share a conserved mode of invasion by actively entering their host cell with the formation of a specialised junction with the host cell membrane and the establishment of the parasite inside a self-induced parasitophorous vacuole (Aikawa *et al.*, 1978). Initial attachment of the parasite to the host cell surface results from low-affinity

**1. Introduction** 

and survival.

**2. Early modifications of the red blood cell** 

*1University Montpellier II, CNRS UMR5235, University Montpellier I, Dynamique des Interactions Membranaires Normales et Pathologiques, 2School of Biological Sciences, Nanyang Technological University, Singapore,* 

**by** *Plasmodium falciparum*

Watanabe, S.; Terashima, K.; Ohta, S., Horibata, S.; Yajima, M.; Shiozawa, Y.; Dewan, M.Z.; Yu, Z.; Ito, M.; Morio, T. et al. (2007). Hematopoietic stem cell-engrafted NOD/SCID/IL2Rgamma null mice develop human lymphoid systems and induce long-lasting HIV-1 infection with specific humoral immune responses. *Blood,* pp 212-218.
