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Infectious Sporozoites of Plasmodium berghei Effectively Activate Liver CD8?+ Dendritic Cells.

ABSTRACT: Immunization with radiation-attenuated sporozoites (RAS) shown to confer complete sterile protection against Plasmodia liver-stage (LS) infection that lasts about 6 to 9?months in mice. We have found that the intermittent infectious sporozoite challenge to immune mice following RAS vaccination extends the longevity of sterile protection by maintaining CD8+ T cell memory responses to LS infection. It is reported that CD8?+ dendritic cells (DCs) are involved in the induction of LS-specific CD8+ T cells following RAS or genetically attenuated parasite (GAP) vaccination. In this study, we demonstrate that CD8?+ DCs respond differently to infectious sporozoite or RAS inoculation. The higher accumulation and activation of CD8?+ DCs was seen in the liver in response to infectious sporozoite 72?h postinoculation and found to be associated with higher expression of chemokines (CCL-20 and CCL-21) and type I interferon response via toll-like receptor signaling in liver. Moreover, the infectious sporozoites were found to induce qualitative changes in terms of the increased MHCII expression as well as costimulatory molecules including CD40 on the CD8?+ DCs compared to RAS inoculation. We have also found that infectious sporozoite challenge increased CD40L-expressing CD4+ T cells, which could help CD8+ T cells in the liver through "licensing" of the antigen-presenting cells. Our results suggest that infectious sporozoite challenge to prior RAS immunized mice modulates the CD8?+ DCs, which might be shaping the fate of memory CD8+ T cells against Plasmodium LS infection.

SUBMITTER: Parmar R

PROVIDER: S-EPMC5809440 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Infectious Sporozoites of Plasmodium berghei Effectively Activate Liver CD8α+ Dendritic Cells.

Parmar Rajesh R Patel Hardik H Yadav Naveen N Parikh Ritika R Patel Khyati K Mohankrishnan Aditi A Bhurani Vishakha V Joshi Urja U Dalai Sarat Kumar SK

Frontiers in immunology 20180208

Immunization with radiation-attenuated sporozoites (RAS) shown to confer complete sterile protection against Plasmodia liver-stage (LS) infection that lasts about 6 to 9 months in mice. We have found that the intermittent infectious sporozoite challenge to immune mice following RAS vaccination extends the longevity of sterile protection by maintaining CD8+ T cell memory responses to LS infection. It is reported that CD8α+ dendritic cells (DCs) are involved in the ind ...[more]

PMID: 29472929

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Project description:In the Plasmodium lifecycle two infectious stages of parasites, merozoites, and sporozoites, efficiently infect mammalian host cells, erythrocytes, and hepatocytes, respectively. The apical structure of merozoites and sporozoites contains rhoptry and microneme secretory organelles, which are conserved with other infective forms of apicomplexan parasites. During merozoite invasion of erythrocytes, some rhoptry proteins are secreted to form a tight junction between the parasite and target cell, while others are discharged to maintain subsequent infection inside the parasitophorous vacuole. It has been questioned whether the invasion mechanisms mediated by rhoptry proteins are also involved in sporozoite invasion of two distinct target cells, mosquito salivary glands and mammalian hepatocytes. Recently we demonstrated that rhoptry neck protein 2 (RON2), which is crucial for tight junction formation in merozoites, is also important for sporozoite invasion of both target cells. With the aim of comprehensively describing the mechanisms of sporozoite invasion, the expression and localization profiles of rhoptry proteins were investigated in Plasmodium berghei sporozoites. Of 12 genes representing merozoite rhoptry molecules, nine are transcribed in oocyst-derived sporozoites at a similar or higher level compared to those in blood-stage schizonts. Immuno-electron microscopy demonstrates that eight proteins, namely RON2, RON4, RON5, ASP/RON1, RALP1, RON3, RAP1, and RAMA, localize to rhoptries in sporozoites. It is noteworthy that most rhoptry neck proteins in merozoites are localized throughout rhoptries in sporozoites. This study demonstrates that most rhoptry proteins, except components of the high-molecular mass rhoptry protein complex, are commonly expressed in merozoites and sporozoites in Plasmodium spp., which suggests that components of the invasion mechanisms are basically conserved between infective forms independently of their target cells. Combined with sporozoite-stage specific gene silencing strategies, the contribution of rhoptry proteins in invasion mechanisms can be described.

Dataset Information

Infectious Sporozoites of Plasmodium berghei Effectively Activate Liver CD8?+ Dendritic Cells.

Publications

Infectious Sporozoites of <i>Plasmodium berghei</i> Effectively Activate Liver CD8α<sup>+</sup> Dendritic Cells.

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