Monocyte-Derived CD11c+ Cells Acquire Plasmodium from Hepatocytes to Prime CD8 T Cell Immunity to Liver-Stage Malaria

Kurup, Samarchith P.; Anthony, Scott M.; Hancox, Lisa S.; Vijay, Rahul; Pewe, Lecia; Moioffer, Steven J; Sompallae, Ramakrishna; Janse, Chris J.; Khan, Shahid M.; Harty, John T.

doi:10.1016/j.chom.2019.02.014

Cited by 53 publications

(72 citation statements)

References 59 publications

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“…to the liver could be studied using HLA tetramers [53,54]. This further justifies the creation of a repository of samples from this trial for additional investigation by others.…”

Section: Plos Onementioning

confidence: 83%

IMRAS—A clinical trial of mosquito-bite immunization with live, radiation-attenuated P. falciparum sporozoites: Impact of immunization parameters on protective efficacy and generation of a repository of immunologic reagents

et al. 2020

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Background Immunization with radiation-attenuated sporozoites (RAS) by mosquito bite provides >90% sterile protection against Plasmodium falciparum (Pf) malaria in humans. RAS invade hepatocytes but do not replicate. CD8+ T cells recognizing parasite-derived peptides on the surface of infected hepatocytes are likely the primary protective mechanism. We conducted a randomized clinical trial of RAS immunization to assess safety, to achieve 50% vaccine efficacy (VE) against controlled human malaria infection (CHMI), and to generate reagents from protected and non-protected subjects for future identification of protective immune mechanisms and antigens. Methods Two cohorts (Cohort 1 and Cohort 2) of healthy, malaria-naïve, non-pregnant adults age 18-50 received five monthly immunizations with infected (true-immunized, n = 21) or noninfected (mock-immunized, n = 5) mosquito bites and underwent homologous CHMI at 3

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“…to the liver could be studied using HLA tetramers [53,54]. This further justifies the creation of a repository of samples from this trial for additional investigation by others.…”

Section: Plos Onementioning

confidence: 83%

IMRAS—A clinical trial of mosquito-bite immunization with live, radiation-attenuated P. falciparum sporozoites: Impact of immunization parameters on protective efficacy and generation of a repository of immunologic reagents

et al. 2020

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“…Plasmodium infection induced a rapid hepatic influx of CD11c + monocyte-derived cells (92). These cells were seen to ingest parasites from dying hepatocytes as early as 40 h postinfection, when the parasites were initially thought to be restricted in hepatocytes (92). After acquiring antigens, these APCs migrated into the liver-draining lymph nodes, where a protective CD8 + T cell response was induced as reported elsewhere (93,94).…”

Section: T Cell Priming In the Liver-how Does A Naive T Cell Become Amentioning

confidence: 58%

“…Not only tissue-resident APCs but also emigrant APCs can prime T cells in the liver. Plasmodium infection induced a rapid hepatic influx of CD11c + monocyte-derived cells (92). These cells were seen to ingest parasites from dying hepatocytes as early as 40 h postinfection, when the parasites were initially thought to be restricted in hepatocytes (92).…”

Section: T Cell Priming In the Liver-how Does A Naive T Cell Become Amentioning

confidence: 99%

Live Imaging of Innate and Adaptive Immune Responses in the Liver

Zeng

2020

Front. Immunol.

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Immune response in the liver is determined by the spatial organization and cellular dynamics of hepatic immune cells. The liver vasculature accommodates abundant tissue-resident innate immune cells, such as Kupffer cells, natural killer cells, and natural killer T cells, to ensure efficient intravascular immunosurveillance. The fenestrated sinusoids also allow direct contact between circulating T cells and non-canonical antigen-presenting cells, such as hepatocytes, to instruct adaptive immune responses. Distinct cellular behaviors are exploited by liver immune cells to exert proper functions. Intravital imaging enables real-time visualization of individual immune cell in living animals, representing a powerful tool in dissecting the spatiotemporal features of intrahepatic immune cells during steady state and liver diseases. This review summarizes current advances in liver immunology prompted by in vivo imaging, with a particular focus on liver-resident innate immune cells and hepatic T cells.

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“…Interaction between DCs and Plasmodium parasite occurs at various points during the life cycle of the parasite in a human host (Figure 1). The parasite encounters DCs in the skin ( Figure 1A) (13,25), the liver ( Figure 1B) (26,27), and the blood and spleen ( Figure 1C) (4). Tissue resident DCs in each of the sites can phagocytose parasite components and initiate specific immune responses to the parasite.…”

Section: Plasmodium Life Cyclementioning

confidence: 99%

The Impact of Malaria Parasites on Dendritic Cell–T Cell Interaction

et al. 2020

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Malaria is caused by apicomplexan parasites of the genus Plasmodium. While infection continues to pose a risk for the majority of the global population, the burden of disease mainly resides in Sub-Saharan Africa. Although immunity develops against disease, this requires years of persistent exposure and is not associated with protection against infection. Repeat infections occur due to the parasite's ability to disrupt or evade the host immune responses. However, despite many years of study, the mechanisms of this disruption remain unclear. Previous studies have demonstrated a parasite-induced failure in dendritic cell (DCs) function affecting the generation of helper T cell responses. These T cells fail to help B cell responses, reducing the production of antibodies that are necessary to control malaria infection. This review focuses on our current understanding of the effect of Plasmodium parasite on DC function, DC-T cell interaction, and T cell activation. A better understanding of how parasites disrupt DC-T cell interactions will lead to new targets and approaches to reinstate adaptive immune responses and enhance parasite immunity.

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Monocyte-Derived CD11c+ Cells Acquire Plasmodium from Hepatocytes to Prime CD8 T Cell Immunity to Liver-Stage Malaria

Cited by 53 publications

References 59 publications

IMRAS—A clinical trial of mosquito-bite immunization with live, radiation-attenuated P. falciparum sporozoites: Impact of immunization parameters on protective efficacy and generation of a repository of immunologic reagents

IMRAS—A clinical trial of mosquito-bite immunization with live, radiation-attenuated P. falciparum sporozoites: Impact of immunization parameters on protective efficacy and generation of a repository of immunologic reagents

Live Imaging of Innate and Adaptive Immune Responses in the Liver

The Impact of Malaria Parasites on Dendritic Cell–T Cell Interaction

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