The Human Spleen in Malaria: Filter or Shelter?

Henry, B.; Roussel, Camille; Carucci, Mario; Brousse, Valentine; Ndour, Papa Alioune; Buffet, Pierre

doi:10.1016/j.pt.2020.03.001

Cited by 35 publications

(34 citation statements)

References 93 publications

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“…In vivo, cytoadherence can lead to sequestration and rosetting in P. falciparum infections, which serve to avoid parasite removal by splenic filtration and increase immune evasion, respectively [14,15]. Therefore, accurate knowledge about these phenomena is critical for understanding Plasmodium virulence.…”

Section: Nutrient Levels Affect Parasite Physiology and Growthmentioning

confidence: 99%

“…While cytoadherence is beneficial in vivo [14], the parasite's effort to avoid host clearance may reflect a fitness cost in the absence of splenic filtration in vitro. The density of PfEMP1 knobs on the RBC surface ( Figure 1B), which mediate sequestration in P. falciparum to avoid physical filtration by the spleen, was reduced fivefold upon adaptation of ex vivo isolates to in vitro culture [31].…”

Section: The Contribution Of Rheologymentioning

confidence: 99%

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From Circulation to Cultivation: Plasmodium In Vivo versus In Vitro

Brown

Guler

2020

Trends in Parasitology

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Research on Plasmodium parasites has driven breakthroughs in reducing malaria morbidity and mortality. Experimental analysis of in vivo/ex vivo versus in vitro samples serve unique roles in Plasmodium research. However, these distinctly different environments lead to discordant biology between parasites in host circulation and those under laboratory cultivation. Here, we review how in vitro factors, such as nutrient levels and physical forces, differ from those in the human host and the resulting implications for parasite growth, survival, and virulence. Additionally, we discuss the current utility of direct-from-host methodologies, which avoid the potentially confounding effects of in vitro cultivation. Finally, we make the case for methodological improvements that will drive research progress of physiologically relevant phenotypes. Highlights Standard in vitro culture environments differ dramatically from in vivo conditions in nutrient levels, hematocrit, and rheology and have lower variability in gas levels and temperature. Nutritional and physical differences lead to pronounced, and often rapid, changes in phenomenon, important for understanding virulence in Plasmodium. Parasite drug sensitivity may be altered due to culture adaptation selection, supraphysiological metabolite concentrations, and in vitro media formulations. Parasites propagated in vitro, versus in vivo, show altered transcriptomic and genomic patterns related to virulence factors, metabolism, gametocytogenesis, and more. Direct-from-host methodologies avoid the impacts of in vitro culture adaptation but limit the types of assessments that can be performed as many experiments either require equipment not readily available in endemic settings or necessitate long-term manipulation.

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Section: Nutrient Levels Affect Parasite Physiology and Growthmentioning

confidence: 99%

Section: The Contribution Of Rheologymentioning

confidence: 99%

From Circulation to Cultivation: Plasmodium In Vivo versus In Vitro

Brown

Guler

2020

Trends in Parasitology

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“…In malaria patients treated with antimalarial drug, remnants of the dead parasites are extracted from RBCs without cell lysis in a process called ‘pitting’. This process has been reported for P. falciparum infection and occurs after the death of intracellular parasites 14 . In patients with severe P. falciparum infection, spleen structure was reported to be severely altered with the WP showing marked architectural disorganization and marked dissociation of the border between the WP and the RP and a relative loss of B cells 29 …”

Section: Splenic Cellular Environmentmentioning

confidence: 76%

“…The splenic microstructure is different between mice and humans: mouse spleens have a marginal zone (MZ), an area between WP and RP, which contains a specialized B‐cell compartment and macrophages. In humans, the MZ structure is absent although MZ B cells are present in an area called the perifollicular, or superficial, zone 4,14 . We will mainly describe the mouse splenic tissue environment, and only briefly comment on human tissue, since studies on human malaria tissue have been sparse due its limited availability.…”

Section: Splenic Cellular Environmentmentioning

confidence: 99%

Host‐pathogen interaction in the tissue environment during Plasmodium blood‐stage infection

Yui

Inoue

2020

Parasite Immunology

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Human malarial infection occurs after an infectious Anopheles mosquito bites. Following the initial liver‐stage infection, parasites transform into merozoites, infecting red blood cells (RBCs). Repeated RBC infection then occurs during the blood‐stage infection, while patients experience various malarial symptoms. Protective immune responses are elicited by this systemic infection, but excessive responses are sometimes harmful for hosts. As parasites infect only RBCs and their immediate precursors during this stage, direct parasite‐host interactions occur primarily in the environment surrounded by endothelial lining of blood vessels. The spleen is the major organ where the immune system encounters infected RBCs, causing immunological responses. Its tissue structure is markedly altered during malarial infection in mice and humans. Plasmodium falciparum parasites inside RBCs express proteins, such as PfEMP‐1 and RIFIN, transported to the RBC surfaces in order to evade immunological attack by sequestering themselves in the peripheral vasculature avoiding spleen or by direct immune cell inhibition through inhibitory receptors. Host cell production of regulatory cytokines IL‐10 and IL‐27 limits excessive immune responses, avoiding tissue damage. The regulation of the protective and inhibitory immune responses through host‐parasite interactions allows chronic Plasmodium infection. In this review, we discuss underlying interaction mechanisms relevant for developing effective strategies against malaria.

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“…Much of the infection biology research for parasites exploiting unrivalled organ chips has so far been focused on the malaria parasite Plasmodium falciparum. The human spleen is an immune sentinel that senses subtle mechanical changes in infected and uninfected red blood cells (RBCs), discriminates between them in malaria-infected subjects, and through this filtering function may regulate parasite biomass and induce clinical signs of malaria such as splenomegaly and anemia [62]. Sequestration of P. falciparum-infected red blood cells (IRBC) in the microcirculation represents a critical event in severe malaria pathogenesis.…”

Section: Fungi and Parasitesmentioning

confidence: 99%

Refining Host-Pathogen Interactions: Organ-on-Chip Side of the Coin

Baddal

Marrazzo

2021

Pathogens

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Bioinspired organ-level in vitro platforms that recapitulate human organ physiology and organ-specific responses have emerged as effective technologies for infectious disease research, drug discovery, and personalized medicine. A major challenge in tissue engineering for infectious diseases has been the reconstruction of the dynamic 3D microenvironment reflecting the architectural and functional complexity of the human body in order to more accurately model the initiation and progression of host–microbe interactions. By bridging the gap between in vitro experimental models and human pathophysiology and providing alternatives for animal models, organ-on-chip microfluidic devices have so far been implemented in multiple research areas, contributing to major advances in the field. Given the emergence of the recent pandemic, plug-and-play organ chips may hold the key for tackling an unmet clinical need in the development of effective therapeutic strategies. In this review, latest studies harnessing organ-on-chip platforms to unravel host–pathogen interactions are presented to highlight the prospects for the microfluidic technology in infectious diseases research.

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The Human Spleen in Malaria: Filter or Shelter?

Cited by 35 publications

References 93 publications

From Circulation to Cultivation: Plasmodium In Vivo versus In Vitro

From Circulation to Cultivation: Plasmodium In Vivo versus In Vitro

Host‐pathogen interaction in the tissue environment during Plasmodium blood‐stage infection

Refining Host-Pathogen Interactions: Organ-on-Chip Side of the Coin

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