Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease

Souza, J. Brian de; Hafalla, Julius Clemence R.; Riley, Eleanor M.; Couper, Kevin N.

doi:10.1017/s0031182009991715

Cited by 190 publications

(179 citation statements)

References 176 publications

(246 reference statements)

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“…(n ϭ 3-5 mice/group). H, percentages of GrzB ϩ CD8 ϩ TCR ϩ T cells infiltrating into the brains of WT or Cnr2 Ϫ/Ϫ mice at day 6 after infection with 5 ϫ 10 4 PbTg OVA. The diagram shows percentages of cells (pregated for CD45 hi expression) (mean Ϯ S.E., n ϭ 6 mice/group).…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid Receptor 2 Modulates Susceptibility to Experimental Cerebral Malaria through a CCL17-dependent Mechanism

Alferink

Specht²,

Arends

et al. 2016

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Cannabinoid Receptor 2 Modulates Susceptibility to Experimental Cerebral Malaria through a CCL17-dependent Mechanism

Alferink

Specht²,

Arends

et al. 2016

Journal of Biological Chemistry

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“…Although sequestration of pRBC in the brain microvessels is observed in the histopathology of human and murine CM and considered the direct cause of the neurological syndrome, it is now clear that excessive production of inflammatory mediators induced in the early stage of malarial infection is the primary mechanism of CM pathogenesis [1,24]. Therefore, adequate function of immune regulation arm, mediated by immunosuppressive cytokines and regulatory immune cells, plays an important role in control of inflammatory response and pathogenesis of CM.…”

Section: Discussionmentioning

confidence: 99%

“…Fluorescent mAbs to mouse leukocyte surface molecules used in flow cytometric analysis, B220 (RA3-6B2), CD21/35 (4E3), CD23 (B3B4), CD5 (53-7.3), CD1d (1B1), IgM (eB121-15F9), IgD (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), CD3 (145-2C11), CD4 (L3T4), CD8 (53-6.7), CD49b (DX5), CD19 (1D3), and Treg-cell staining kit were purchased from eBioscience (CA, USA). PE-conjugated anti-mouse IL-10 mAb (JES5-16E3) was obtained from BD Biosciences.…”

Section: Flow Cytometrymentioning

confidence: 99%

Role of IL‐10‐producing regulatory B cells in control of cerebral malaria in Plasmodium berghei infected mice

Liu

Chen

et al. 2013

Eur J Immunol

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IntroductionMalaria caused by infection with protozoan parasites of Plasmodium spp. is one of the most serious infectious diseases of humans and causes about one million deaths annually. Plasmodium infection may induce multiple disease syndromes including severe anemia, metabolic acidosis, and neurological dysfunction, e.g. cerebral malaria (CM) [1]. Sequestration of the Correspondence: Dr. Zhong Su e-mail: su_zhong@gibh.ac.cn parasitized red blood cells (pRBCs) in brain microvessels is a characteristic histopathology feature observed in human and murine CM and is believed to be the primary cause of the neurological syndrome [2,3]. Evidence from more recent studies supports the notion that CM is an immune-driven pathology. The proinflammatory cytokines and mediators produced in the "cytokine storm" during malaria induce activation and recruitment of cytotoxic CD8 + cells in brain blood vessels and upregulate the expression of adhesion receptors by brain endothelial cells, leading to leukocyte accumulation and capillary obstruction, cerebral hemorrhage, and hypoxia in brain tissues [1,[4][5][6]. Therefore, the immune regulatory cells and cytokines may be critical in counteracting the inflammatory response and prevention of malaria-associated www.eji-journal.eu 2908 Yunfeng Liu et al. Eur. J. Immunol. 2013. 43: 2907-2918 neuropathology. The levels of anti-inflammatory cytokines such as IL-10 and TGF-β have been shown to be inversely associated with the occurrence of CM in murine malaria [7,8]. However, no consensus has been reached concerning the role of regulatory T (Treg) cells in regulation of CM pathogenesis [9][10][11].B cells have been traditionally considered antibody-producing cell and APC. Many studies in recent years showed the existence of a subset of B cells that exhibit the immune regulatory functions (reviewed in [12]). An early study by Fillatreau et al.[13] reported a subset of B cells that produce IL-10 and inhibit the immune pathology in murine EAE. Further studies revealed that these regulatory B (Breg) cells play important roles in control of immunopathology in autoimmune diseases [14], cancer [15], and organ transplantation [16]. Breg cells have also been shown to modulate immune responses and immunopathology in infectious diseases. Protective immunities against Salmonella typhimurium and Brucella abortus infections were inhibited by transfer of Breg cells in mouse models [17,18]. Transfer of CD1d + CD5 hi Breg cells rendered the BALB/c mice more susceptible to Leishmania major infection [19]. Adoptive transfer of IL-10-producing B cells isolated from helminth-infected mice inhibited the allergic responses and autoimmune inflammation in recipient mice [20]. Thus, Breg cells are an important component of immunoregulatory system and plays critical roles in immune homeostasis.The immunomodulatory roles of Breg cells have been studied in autoimmune and infectious disease settings, but little is known of its role in regulation of immune response and immunopathology of malaria. In this study, we i...

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“…Infection of C57BL/6 mice with Plasmodium berghei ANKA mimics human symptoms and is arguably the best murine model for this disease complication, termed experimental cerebral malaria (ECM) (3). It has been demonstrated in this model that cerebral pathology is caused by a complicated systemic inflammatory Th1 response involving both innate and adaptive cellular immunity, and a crucial role for both parasitemia and parasite Ag presentation has been demonstrated (4).…”

Section: H Uman Cerebral Malaria (Hcm) Is a Lethal Complication Ofmentioning

confidence: 99%

Chemical Attenuation of Plasmodium in the Liver Modulates Severe Malaria Disease Progression

Lewis

Behrends

Cunha

et al. 2015

The Journal of Immunology

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Cerebral malaria is one of the most severe complications of malaria disease, attributed to a complicated series of immune reactions in the host. The syndrome is marked by inflammatory immune responses, margination of leukocytes, and parasitized erythrocytes in cerebral vessels leading to breakdown of the blood–brain barrier. We show that chemical attenuation of the parasite at the very early, clinically silent liver stage suppresses parasite development, delays the time until parasites establish blood-stage infection, and provokes an altered host immune response, modifying immunopathogenesis and protecting from cerebral disease. The early response is proinflammatory and cell mediated, with increased T cell activation in the liver and spleen, and greater numbers of effector T cells, cytokine-secreting T cells, and proliferating, proinflammatory cytokine-producing T cells. Dendritic cell numbers, T cell activation, and infiltration of CD8+ T cells to the brain are decreased later in infection, possibly mediated by the anti-inflammatory cytokine IL-10. Strikingly, protection can be transferred to naive animals by adoptive transfer of lymphocytes from the spleen at very early times of infection. Our data suggest that a subpopulation belonging to CD8+ T cells as early as day 2 postinfection is responsible for protection. These data indicate that liver stage–directed early immune responses can moderate the overall downstream host immune response and modulate severe malaria outcome.

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Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease

Cited by 190 publications

References 176 publications

Cannabinoid Receptor 2 Modulates Susceptibility to Experimental Cerebral Malaria through a CCL17-dependent Mechanism

Cannabinoid Receptor 2 Modulates Susceptibility to Experimental Cerebral Malaria through a CCL17-dependent Mechanism

Role of IL‐10‐producing regulatory B cells in control of cerebral malaria in Plasmodium berghei infected mice

Chemical Attenuation of Plasmodium in the Liver Modulates Severe Malaria Disease Progression

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