The Time Course of Selected Malarial Infections in Cytokine-Deficient Mice

Heyde, Henri C. van der; Pepper, Barbara J.; Batchelder, Joan; Cigel, Francine; Weidanz, William P.

doi:10.1006/expr.1996.4132

Cited by 98 publications

(87 citation statements)

References 39 publications

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“…High levels of IFN-␥ were indeed produced in normal spz-immunized mice after sporozoite challenge, and in a preliminary experiment we observed that CD4 ϩ T cells were the main source of IFN-␥ (data not shown). It has been shown previously that P. yoelii blood stages are susceptible to the action of this cytokine (38,39), and evidence that infection by this parasite can be controlled by T cells and that they are high producers of IFN-␥ has been obtained recently (40 -42).…”

Section: Discussionmentioning

confidence: 97%

Protective T Cell Immunity against Malaria Liver Stage after Vaccination with Live Sporozoites under Chloroquine Treatment

Belnoue

Costa

Frankenberg

et al. 2004

The Journal of Immunology

211

281

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In this study we present the first systematic analysis of the immunity induced by normal Plasmodium yoelii sporozoites in mice. Immunization with sporozoites, which was conducted under chloroquine treatment to minimize the influence of blood stage parasites, induced a strong protection against a subsequent sporozoite and, to a lesser extent, against infected RBC challenges. The protection induced by this immunization protocol proved to be very effective. Induction of this protective immunity depended on the presence of liver stage parasites, as primaquine treatment concurrent with sporozoite immunization abrogated protection. Protection was not found to be mediated by the Abs elicited against pre-erythrocytic and blood stage parasites, as demonstrated by inhibition assays of sporozoite penetration or development in vitro and in vivo assays of sporozoite infectivity or blood stage parasite development. CD4+ and CD8+ T cells were, however, responsible for the protection through the induction of IFN-γ and NO.

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Section: Discussionmentioning

confidence: 97%

Protective T Cell Immunity against Malaria Liver Stage after Vaccination with Live Sporozoites under Chloroquine Treatment

Belnoue

Costa

Frankenberg

et al. 2004

The Journal of Immunology

211

281

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“…Tfh cells secrete several cytokines, such as IFN-g, IL-2, IL-4, and IL-21. IL-2-, IL-4-, and IFN-g-deficient mice experience more exacerbated relapses of parasitemia than do WT mice, but are eventually able to control the infection (86,87). However, IL-21 KO mice are unable to control P. chabaudi parasitemia (88).…”

Section: Discussionmentioning

confidence: 99%

Development of a Novel CD4+ TCR Transgenic Line That Reveals a Dominant Role for CD8+ Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria

Fernandez‐Ruiz

Lau

Ghazanfari

et al. 2017

The Journal of Immunology

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We describe an MHC class II (I-Ab)–restricted TCR transgenic mouse line that produces CD4+ T cells specific for Plasmodium species. This line, termed PbT-II, was derived from a CD4+ T cell hybridoma generated to blood-stage Plasmodium berghei ANKA (PbA). PbT-II cells responded to all Plasmodium species and stages tested so far, including rodent (PbA, P. berghei NK65, Plasmodium chabaudi AS, and Plasmodium yoelii 17XNL) and human (Plasmodium falciparum) blood-stage parasites as well as irradiated PbA sporozoites. PbT-II cells can provide help for generation of Ab to P. chabaudi infection and can control this otherwise lethal infection in CD40L-deficient mice. PbT-II cells can also provide help for development of CD8+ T cell–mediated experimental cerebral malaria (ECM) during PbA infection. Using PbT-II CD4+ T cells and the previously described PbT-I CD8+ T cells, we determined the dendritic cell (DC) subsets responsible for immunity to PbA blood-stage infection. CD8+ DC (a subset of XCR1+ DC) were the major APC responsible for activation of both T cell subsets, although other DC also contributed to CD4+ T cell responses. Depletion of CD8+ DC at the beginning of infection prevented ECM development and impaired both Th1 and follicular Th cell responses; in contrast, late depletion did not affect ECM. This study describes a novel and versatile tool for examining CD4+ T cell immunity during malaria and provides evidence that CD4+ T cell help, acting via CD40L signaling, can promote immunity or pathology to blood-stage malaria largely through Ag presentation by CD8+ DC.

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“…IFN-␥R Ϫ/Ϫ 129 ϫ C57BL/6 mice cleared blood-stage nonlethal parasite infection with only a slight delay compared with WT mice (52), and recombinant IFN-␥ treatment did not alter the course of PyNL infection (47). In contrast, IFN-␥ Ϫ/Ϫ mice on a C57BL/6 ϫ 129 background were unable to clear PyNL infections (56). Moreover, recombinant IFN-␥ protected SW, BALB/c, and CBA mice against PyL infection (47), and mice treated with anti-IFN-␥ antibodies succumbed earlier to lethal P. yoelii infection but had parasite levels similar to those of control mice (21).…”

Section: Discussionmentioning

confidence: 99%

“…7C and D). However, given the essential role of IFN-␥ in controlling nonlethal P. chabaudi infection (28,31,51,56) and in preventing cerebral malaria in P. berghei K173 infection (30), it was rather unexpected to find that during PyNL infection, the course of infection was essentially identical in WT and IFN-␥ Ϫ/Ϫ mice (Fig. 7B, C, and D).…”

Section: Vol 75 2007 Control Of Lethal and Nonlethal P Yoelii Infementioning

confidence: 98%

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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The Time Course of Selected Malarial Infections in Cytokine-Deficient Mice

Cited by 98 publications

References 39 publications

Protective T Cell Immunity against Malaria Liver Stage after Vaccination with Live Sporozoites under Chloroquine Treatment

Protective T Cell Immunity against Malaria Liver Stage after Vaccination with Live Sporozoites under Chloroquine Treatment

Development of a Novel CD4+ TCR Transgenic Line That Reveals a Dominant Role for CD8+ Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria

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

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