The role of intrahepatic lymphocytes in mediating protective immunity induced by attenuated Plasmodium berghei sporozoites

Krzych, Urszula; Schwenk, Robert; Guebre‐Xabier, Mimi; Sun, Peifang; Palmer, Dupeh R.; White, Katherine; Chalom, Isaac

doi:10.1034/j.1600-0528.2002.00013h.x

Cited by 52 publications

(48 citation statements)

References 43 publications

(57 reference statements)

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“…[5][6][7][8][9] Our previous [1][2][3] and present data support these findings. In the case of human malaria, CD36 antigens (sequestrin) on erythrocytes are known to mediate adherence and subsequent infection of Plasmodium falciparum.…”

Section: Discussionsupporting

confidence: 81%

Protection against malaria by anti‐erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites

et al. 2005

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SummaryWe have previously reported that erythropoiesis commences in the liver and spleen after malarial infection, and that newly generated erythrocytes in the liver are essential for infection of malarial parasites as well as continuation of infection. At this time, erythropoietin (EPO) is elevated in the serum. In the present study, we administered EPO or anti-EPO antibody into C57BL/6 (B6) mice to modulate the serum level of EPO. When mice were infected with a non-lethal strain (17NXL) of Plasmodium yoelii (blood-stage infection of 10 4 parasitized erythrocytes per mouse), parasitemia continued for 1 month, showing a peak at day 17. Daily injection of EPO (200 IU/day per mouse) from day five to day 14 prolonged parasitemia, whereas injection of anti-EPO antibody (1.5 mg/day per mouse) every second day from day five to day 28 decreased it. Erythropoiesis was confirmed in the liver, spleen and bone marrow by the appearance of nucleated erythrocytes (TER119+). When anti-EPO antibody was injected by the same protocol into mice infected with a lethal strain (17XL) of P. yoelii , all mice showed decreased parasitemia and recovered from the infection. These results suggest that the use of anti-EPO antibody after malarial infection may be of therapeutic value in severe cases of malaria.

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Section: Discussionsupporting

confidence: 81%

Protection against malaria by anti‐erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites

et al. 2005

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“…Recent studies have proposed that as IrrSpz enter the liver and invade hepatocytes, parasite-derived antigens may be taken up by antigen-presenting cells in this organ, leading to the induction of protective immunity [19,20].…”

Section: Discussionmentioning

confidence: 99%

Priming of CD8⁺ T cell responses following immunization with heat‐killed Plasmodium sporozoites

et al. 2006

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Protective immune responses against malaria are induced by immunization with radiation-attenuated Plasmodium sporozoites. In contrast, non-viable, heat-killed sporozoites do not induce protection, emphasizing the requirement for live parasites to achieve effective immune responses. Using an experimental system with CD8 + T cells from T cell receptor-transgenic mice, we analyzed the primary CD8 + T cell responses elicited by heat-killed inactivated sporozoites. We found that the numbers of specific CD8 + T cells induced were much lower compared to when immunizing with attenuated sporozoites; however, the kinetics of activation and the phenotype of these T cells were similar in both groups. Despite their low frequency after priming, high numbers of specific CD8 + T cells were observed after boosting with a recombinant vaccinia virus. Upon induction of the recall response, the same level of protection was observed when either heat-killed or attenuated sporozoites were used for priming. We propose that live parasites are not critical for the induction of memory T cell populations against the malaria liver stages.

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“…We suggested [14] that the tolerogenic milieu in the liver [15,16] favors Plasmodia spz colonization of and schizogony in hepatocytes; however, if c-spz induce a local liver inflammation, the reversal of tolerance might facilitate induction of protective immunity. Therefore, we hypothesize that unlike naive KC, c-spz-immune KC would respond to infectious spz in a manner characteristic of protective immunity, i.e.…”

Section: Introductionmentioning

confidence: 98%

The immune status of Kupffer cells profoundly influences their responses to infectiousPlasmodium berghei sporozoites

Steers

Schwenk

Bacon³

et al. 2005

Eur. J. Immunol.

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Multi-factorial immune mechanisms underlie protection induced with radiationattenuated Plasmodia sporozoites (c-spz). Spz pass through Kupffer cells (KC) before invading hepatocytes but the involvement of KC in protection is poorly understood. In this study we investigated whether c-spz-immune KC respond to infectious spz in a manner that is distinct from the response of naive KC to infectious spz. KC were isolated from (1) naive, (2) spz-infected, (3) c-spz-immune, and (4) c-spz-immune-challenged C57BL/6 mice and examined for the expression of MHC class I and II, CD40 and CD80/CD86, IL-10 and IL-12 responses and antigen-presenting cell (APC) function. KC from c-spz-immune-challenged mice up-regulated class I and costimulatory molecules and produced elevated IL-12p40, relative to naive KC. In contrast, KC from naive mice exposed to infectious spz down-modulated class I and IL-12p40 was undetectable. Accordingly, KC from spz-infected mice had reduced APC function, while KC from c-spz-immune-challenged mice exhibited augmented APC activity. The nearly opposite responses are consistent with the fact that spz challenge of c-spz-immune mice results in long-lasting sterile protection, while infection of naive mice always results in malaria.

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The role of intrahepatic lymphocytes in mediating protective immunity induced by attenuated Plasmodium berghei sporozoites

Cited by 52 publications

References 43 publications

Protection against malaria by anti‐erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites

Protection against malaria by anti‐erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites

Priming of CD8⁺ T cell responses following immunization with heat‐killed Plasmodium sporozoites

The immune status of Kupffer cells profoundly influences their responses to infectiousPlasmodium berghei sporozoites

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The role of intrahepatic lymphocytes in mediating protective immunity induced by attenuated Plasmodium berghei sporozoites

Cited by 52 publications

References 43 publications

Protection against malaria by anti‐erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites

Protection against malaria by anti‐erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites

Priming of CD8+ T cell responses following immunization with heat‐killed Plasmodium sporozoites

The immune status of Kupffer cells profoundly influences their responses to infectiousPlasmodium berghei sporozoites

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Priming of CD8⁺ T cell responses following immunization with heat‐killed Plasmodium sporozoites