Mouse Models of Blood-Stage Malaria Infections: Immune Responses and Cytokines Involved in Protection and Pathology

Langhorne, Jean; Quin, Stuart; Sanni, Latifu A.

doi:10.1159/000058845

Cited by 146 publications

(148 citation statements)

References 129 publications

(129 reference statements)

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“…The results of the present study provide an additional plausible scenario for the activation of P2X 7 in vivo, i.e., by NAD ϩ and ATP released during hemolysis. Malaria, for example, is associated with periodic hemolysis and complex changes in T cell function and apoptosis (47,78). It will, therefore, be of interest to determine whether and to what extent the genetic ablation or pharmacological inhibition of ART2 and/or P2X 7 affects disease progression in murine malaria models.…”

Section: Discussionmentioning

confidence: 99%

NAD+ and ATP Released from Injured Cells Induce P2X7-Dependent Shedding of CD62L and Externalization of Phosphatidylserine by Murine T Cells

Scheuplein

Schwarz²,

Adriouch

et al. 2009

The Journal of Immunology

114

136

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Extracellular NAD+ and ATP trigger the shedding of CD62L and the externalization of phosphatidylserine on murine T cells. These events depend on the P2X7 ion channel. Although ATP acts as a soluble ligand to activate P2X7, gating of P2X7 by NAD+ requires ecto-ADP-ribosyltransferase ART2.2-catalyzed transfer of the ADP-ribose moiety from NAD+ onto Arg125 of P2X7. Steady-state concentrations of NAD+ and ATP in extracellular compartments are highly regulated and usually are well below the threshold required for activating P2X7. The goal of this study was to identify possible endogenous sources of these nucleotides. We show that lysis of erythrocytes releases sufficient levels of NAD+ and ATP to induce activation of P2X7. Dilution of erythrocyte lysates or incubation of lysates at 37°C revealed that signaling by ATP fades more rapidly than that by NAD+. We further show that the routine preparation of primary lymph node and spleen cells induces the release of NAD+ in sufficient concentrations for ART2.2 to ADP-ribosylate P2X7, even at 4°C. Gating of P2X7 occurs when T cells are returned to 37°C, rapidly inducing CD62L-shedding and PS-externalization by a substantial fraction of the cells. The “spontaneous” activation of P2X7 during preparation of primary T cells could be prevented by i.v. injection of either the surrogate ART substrate etheno-NAD or ART2.2-inhibitory single domain Abs 10 min before sacrificing mice.

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Section: Discussionmentioning

confidence: 99%

NAD+ and ATP Released from Injured Cells Induce P2X7-Dependent Shedding of CD62L and Externalization of Phosphatidylserine by Murine T Cells

Scheuplein

Schwarz²,

Adriouch

et al. 2009

The Journal of Immunology

114

136

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“…Given the overwhelming evidence for a crucial role for IFN-␥ in controlling acute murine malaria infections (23,25,54), we considered the possibility that failure to produce IFN-␥ in the initial few days of lethal P. yoelii infection might explain the very rapid parasite growth. In apparent support of this possibility, and consistent with patterns of NK activation, an early burst of IFN-␥ was observed in the plasma of PyNL-infected (but not PyL-infected) mice on day 1 p.i.…”

Section: P Yoelii-induced T-cell Hyporesponsiveness Is Both Cd11bmentioning

confidence: 99%

“…Proinflammatory cytokines are essential for the control of intraerythrocytic Plasmodium infections in humans and in experimental animals (23,25,54). Antigen-presenting cells (APCs) produce interleukin 12 (IL-12), IL-15, IL-18, and tumor necrosis factor alpha (TNF-␣) (17,26,31,32,37,38,40,44,45,48), which can rapidly activate cells of the innate immune system to produce gamma interferon (IFN-␥) (31,32,44,64).…”

mentioning

confidence: 99%

Macrophage-Mediated but Gamma Interferon-Independent Innate Immune Responses Control the Primary Wave ofPlasmodium yoeliiParasitemia

et al. 2007

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In most models of blood-stage malaria infection, proinflammatory immune responses are required for control of infection and elimination of parasites. We hypothesized therefore that the fulminant infections caused in mice by the lethal strain of Plasmodium yoelii (17XL) might be due to failure to activate a sufficient inflammatory response. Here we have compared the adaptive CD4 ؉ T-cell and innate immune response to P. yoelii 17XL with that induced by the self-resolving, nonlethal strain of P. yoelii, 17X(NL). During the first 7 to 9 days of infection, splenic effector CD4 ؉ T-cell responses were similar in mice with lethal and nonlethal infections with similar levels of activation in vivo and equivalent proliferation in vitro following mitogenic stimulation. Nonspecific T-cell hyporesponsiveness was observed at similar levels during both infections and was due, in part, to suppression mediated by CD11b ؉ cells. Importantly, however, RAG ؊/؊ mice were able to control the initial growth phase of nonlethal P. yoelii infection as effectively as wild-type mice, indicating that T cells and/or B cells play little, if any, role in control of the primary peak of parasitemia. Somewhat unexpectedly, we could find no clear role for either NK cells or gamma interferon (IFN-␥) in controlling primary P. yoelii infection. In contrast, depletion of monocytes/macrophages exacerbated parasite growth and anemia during both lethal and nonlethal acute P. yoelii infections, indicating that there is an IFN-␥-, NK cell-, and T-cell-independent pathway for induction of effector macrophages during acute malaria infection.

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“…This rodent malaria has many features in common with human disease (Cox et al 1987, Gilks et al 1990, Mackinnon et al 2002 and has been used extensively in laboratory research on malaria (Barclay et al 2012, Schneider et al 2012, Spence et al 2012, Cameron et al 2013, Waisberg et al 2013. Infection with P. c. chabaudi AS is typically self-resolving in C57BL/6 mice; however, it is lethal in A/J mice (Langhorne et al 2002). The mechanisms for this phenomenon have been extensively investigated (Langhorne et al 1989, Stevenson et al 1990, 1995, Stevenson and Tam 1993, Sam and Stevenson 1999 and it is widely accepted that the different outcomes are due to balance and timing of the Th1 and Th2 immune responses (Taylor-Robinson et al 1993).…”

Section: Foxp3mentioning

confidence: 99%

Bacillus Calmette-Guerin-inoculation at different time points influences the outcome of C57BL/6 mice infected with Plasmodium chabaudi chabaudi AS

Cao¹,

Wang²,

Liu³

et al. 2016

FOLIA PARASIT

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Bacillus Calmette-Guérin (BCG) is an attenuated Mycobacterium tuberculosis vaccine. We performed a series of co-infection experiments with BCG-Plasmodium chabaudi chabaudi Landau, 1965 AS using C57BL/6 mice to analyse whether BCG can affect the development of protective immunity to infection with Plasmodium spp. and the mechanism of this protection. We divided mice into four groups: BCG-inoculation 4 weeks prior to P. c. chabaudi AS infection (B-4w-Pc); simultaneous BCG-inoculation and P. c. chabaudi AS infection (Pc+B); BCG-inoculation 3 days post P. c. chabaudi AS (Pc-3-B) infection; and mono-P. c. chabaudi AS infection as control (Pc). The parasitemia level in the B-4w-Pc group was noticeably higher than control group at 6-19 days post infection (dpi). Compared with the control group, the proportion of CD4 ) in the B-4w-Pc group than the control group at all the time points post infection and the expression of MHC II was noticeably reduced on day 8 pi. Our findings confirmed that BCG inoculation prior to Plasmodium infection resulted in excessive activation and proliferation of Tregs and upregulation of anti-inflammatory mediators, which inhibited establishment of a Th1-dominant immune response during the early stages of Plasmodium infection by inhibiting dendritive cells response. BCG inoculation prior to P. c. chabaudi AS infection may contribute to overgrowth of parasites as well as mortality in mice.

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Mouse Models of Blood-Stage Malaria Infections: Immune Responses and Cytokines Involved in Protection and Pathology

Cited by 146 publications

References 129 publications

NAD+ and ATP Released from Injured Cells Induce P2X7-Dependent Shedding of CD62L and Externalization of Phosphatidylserine by Murine T Cells

NAD+ and ATP Released from Injured Cells Induce P2X7-Dependent Shedding of CD62L and Externalization of Phosphatidylserine by Murine T Cells

Macrophage-Mediated but Gamma Interferon-Independent Innate Immune Responses Control the Primary Wave ofPlasmodium yoeliiParasitemia

Bacillus Calmette-Guerin-inoculation at different time points influences the outcome of C57BL/6 mice infected with Plasmodium chabaudi chabaudi AS

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