Host cell cytosolic immune response during Plasmodium liver stage development

Agop‐Nersesian, Carolina; Niklaus, Livia; Wacker, Rahel; Heussler, Volker

doi:10.1093/femsre/fuy007

Cited by 46 publications

(81 citation statements)

References 94 publications

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“…While the events that lead to this elimination are unknown, it is tempting to speculate that the parasites that have not been able to manipulate their intracellular environment effectively, lose the fight for survival with the host cell. Indeed, very late stage parasites eventually lose autophagy markers from their PVM, which is a required step, since those that do not lose these markers show impaired growth and do not complete liver stage development …”

Section: Synopsismentioning

confidence: 99%

Melanin processing by keratinocytes: A non‐microbial type of host‐pathogen interaction?

Moreiras

Silva

Seabra

et al. 2019

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The mechanisms that regulate skin pigmentation have been the subject of intense research in recent decades. In contrast with melanin biogenesis and transport within melanocytes, little is known about how melanin is transferred and processed within keratinocytes. Several models have been proposed for how melanin is transferred, with strong evidence supporting coupled exo/endocytosis. Recently, two reports suggest that upon internalization, melanin is stored within keratinocytes in an arrested compartment, allowing the pigment to persist for long periods. In this commentary, we identify a striking parallelism between melanin processing within keratinocytes and the host-pathogen interaction with Plasmodium, opening new avenues to understand the complex molecular mechanisms that ensure skin pigmentation and photoprotection. K E Y W O R D S autophagy, endocytic pathway, melanin, membrane traffic, Plasmodium, UV-radiation 1 | SYNOPSIS Melanin processing within keratinocytes remains elusive. Recent reports suggest that melanin escapes degradation and remains in an arrested compartment inside keratinocytes for long periods. In this commentary, we highlight the similarities between melanin processing and the host-pathogen interaction that occurs with Plasmodium during liver infection and point out some of the most important questions yet to be answered. The skin is the largest organ of the human body and alongside its barrier properties against external aggressions, it has an important ultraviolet (UV)-protective function. The superficial layer, the epidermis is composed by two main cell types: keratinocytes and melanocytes. Keratinocytes form a stratified epithelium differentiating from the basal layer to the cornified superficial layers. Melanocytes are residents of the basal layer and are responsible for the synthesis, packaging and transfer of the pigment melanin to neighboring keratinocytes.Photoprotection is achieved by the polarization of melanin around the nucleus of keratinocytes, forming a supra-nuclear melanin cap or "parasol" on the sun-exposed side, effectively protecting the nuclear DNA from UV-induced damage. 1 Skin pigmentation is, therefore the result of a cross-talk between melanocytes and keratinocytes, where melanocytes are pigment-producers and keratinocytes are pigment- recipients. 2Melanosome biogenesis is initiated at the perinuclear region and undergoes a process of organelle maturation, whereas fully mature melanosomes tend to accumulate at the tips of melanocyte dendrites. 3 When fully mature and located at the tips of melanocyte dendrites, melanin is transferred to keratinocytes. The actual mechanism of melanin transfer remains controversial. Recently, we proposed that the predominant model of melanin transfer is coupled exo/endocytosis where the melanin core or "melanocore" is exocytosed by melanocytes and then internalized by keratinocytes. 4Regardless of the transfer mechanism, melanin is processed within keratinocytes and ends up forming a well-described supranuclear cap, polarized to the s...

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Section: Synopsismentioning

confidence: 99%

Melanin processing by keratinocytes: A non‐microbial type of host‐pathogen interaction?

Moreiras

Silva

Seabra

et al. 2019

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“…After sporozoites enter the hepatocyte cytoplasm, they form a parasite vacuolar membrane that interfaces with the host autophagy system [35][36][37]. Parasites have designed a system to escape this endogenous cytoplasmic immunity that involves disrupting autophagy and lysosome interactions with the parasitophorous vacuole membrane (PVM) [38]. Specifically, the parasite tubovesicular network can sequester host factors that damage the PVM [37].…”

Section: Discussionmentioning

confidence: 99%

Identification of Plasmodium falciparum proteoforms from liver stage models

Winer

Edgel

Zou

et al. 2020

Malar J

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Background: Immunization with attenuated malaria sporozoites protects humans from experimental malaria challenge by mosquito bite. Protection in humans is strongly correlated with the production of T cells targeting a heterogeneous population of pre-erythrocyte antigen proteoforms, including liver stage antigens. Currently, few T cell epitopes derived from Plasmodium falciparum, the major aetiologic agent of malaria in humans are known. Methods:In this study both in vitro and in vivo malaria liver stage models were used to sequence host and pathogen proteoforms. Proteoforms from these diverse models were subjected to mild acid elution (of soluble forms), multi-dimensional fractionation, tandem mass spectrometry, and top-down bioinformatics analysis to identify proteoforms in their intact state. Results:These results identify a group of host and malaria liver stage proteoforms that meet a 5% false discovery rate threshold. Conclusions:This work provides proof-of-concept for the validity of this mass spectrometry/bioinformatic approach for future studies seeking to reveal malaria liver stage antigens towards vaccine development.

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“…Plasmodium parasites undergo a dramatic amplification during the liver stage of their life cycle, when an individual sporozoite infecting a hepatocyte multiplies inside a parasitophorous vacuole (PV) to produce several thousand infective merozoites (Prudencio et al, 2006;Vaughan and Kappe, 2017). This rapid intra-hepatic growth requires extensive networking and interactions with the host's liver cells, at both the sub-cellular and molecular levels (Agop-Nersesian et al, 2018;Nyboer et al, 2018). Pioneering ultrastructure studies employing sporozoite infection of a restricted area of rat livers have suggested extensive interactions of the PV membrane (PVM) with different host organelles during parasite development (Meis et al, 1981(Meis et al, , 1983aShin et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

Association of Plasmodium berghei With the Apical Domain of Hepatocytes Is Necessary for the Parasite's Liver Stage Development

Balasubramanian

Zuzarte‐Luís

Syed

et al. 2020

Front. Cell. Infect. Microbiol.

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Plasmodium parasites undergo a dramatic transformation during the liver stage of their life cycle, amplifying over 10,000-fold inside infected hepatocytes within a few days. Such a rapid growth requires large-scale interactions with, and manipulations of, host cell functions. Whereas hepatocyte polarity is well-known to be critical for liver function, little is presently known about its involvement during the liver stage of Plasmodium development. Apical domains of hepatocytes are critical components of their polarity machinery and constitute the bile canalicular network, which is central to liver function. Here, we employed high resolution 3-D imaging and advanced image analysis of Plasmodium-infected liver tissues to show that the parasite associates preferentially with the apical domain of hepatocytes and induces alterations in the organization of these regions, resulting in localized changes in the bile canalicular architecture in the liver tissue. Pharmacological perturbation of the bile canalicular network by modulation of AMPK activity reduces the parasite's association with bile canaliculi and arrests the parasite development. Our findings using Plasmodium-infected liver tissues reveal a host-Plasmodium interaction at the level of liver tissue organization. We demonstrate for the first time a role for bile canaliculi, a central component of the hepatocyte polarity machinery, during the liver stage of Plasmodium development.

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Host cell cytosolic immune response during Plasmodium liver stage development

Cited by 46 publications

References 94 publications

Melanin processing by keratinocytes: A non‐microbial type of host‐pathogen interaction?

Melanin processing by keratinocytes: A non‐microbial type of host‐pathogen interaction?

Identification of Plasmodium falciparum proteoforms from liver stage models

Association of Plasmodium berghei With the Apical Domain of Hepatocytes Is Necessary for the Parasite's Liver Stage Development

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