The role of the spleen in malaria

Portillo, Hernando A. del; Ferrer, M. Carmen Olivé; Brugat, Thibaut; Martín-Jaular, Lorena; Langhorne, Jean; Lacerda, Marcus Vinícius Guimarães

doi:10.1111/j.1462-5822.2011.01741.x

Cited by 182 publications

(170 citation statements)

References 101 publications

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“…41 Inflammation and hyperplasia, seen during Plasmodium infection can impair blood flow through the spleen and lead to organ failure. 42 In the absence of infection, ABA treatment significantly decreased the number of sinusoidal leukocytes in the liver; this trend, although not significant, was also evident in P. yoelii-infected mice (Figure 2A and E). In P. yoeliiinfected mice, hemozoin deposition, pigment, portal tract inflammation, extramedullary hematopoeisis, and Kupffer cell density were increased relative to controls, but these levels were not altered by ABA treatment (Supplemental Figure 3A).…”

Section: Resultsmentioning

confidence: 78%

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Glennon¹,

Adams²,

Hicks³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Nearly half of the world's population is at risk for malaria. Increasing drug resistance has intensified the need for novel therapeutics, including treatments with intrinsic transmission-blocking properties. In this study, we demonstrate that the isoprenoid abscisic acid (ABA) modulates signaling in the mammalian host to reduce parasitemia and the formation of transmissible gametocytes and in the mosquito host to reduce parasite infection. Oral ABA supplementation in a mouse model of malaria was well tolerated and led to reduced pathology and enhanced gene expression in the liver and spleen consistent with infection recovery. Oral ABA supplementation also increased mouse plasma ABA to levels that can signal in the mosquito midgut upon blood ingestion. Accordingly, we showed that supplementation of a Plasmodium falciparum-infected blood meal with ABA increased expression of mosquito nitric oxide synthase and reduced infection prevalence in a nitric oxide-dependent manner. Identification of the mechanisms whereby ABA reduces parasite growth in mammals and mosquitoes could shed light on the balance of immunity and metabolism across eukaryotes and provide a strong foundation for clinical translation.

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Section: Resultsmentioning

confidence: 78%

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Glennon¹,

Adams²,

Hicks³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…A number of potential innate control mechanisms have been suggested. In particular, the mechanical removal of pRBCs by the spleen (8,(15)(16)(17)(18) [or liver (19)] is believed to be a primary mechanism by which the host controls the PMF (12). However, few studies have attempted to directly measure host removal of pRBCs in vivo (13,19).…”

mentioning

confidence: 99%

Host-mediated impairment of parasite maturation during blood-stage Plasmodium infection

Khoury

Cromer

Akter

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Severe malaria and associated high parasite burdens occur more frequently in humans lacking robust adaptive immunity to Plasmodium falciparum. Nevertheless, the host may partly control blood-stage parasite numbers while adaptive immunity is gradually established. Parasite control has typically been attributed to enhanced removal of parasites by the host, although in vivo quantification of this phenomenon remains challenging. We used a unique in vivo approach to determine the fate of a single cohort of semisynchronous, Plasmodium berghei ANKA-or Plasmodium yoelii 17XNL-parasitized red blood cells (pRBCs) after transfusion into naive or acutely infected mice. As previously shown, acutely infected mice, with ongoing splenic and systemic inflammatory responses, controlled parasite population growth more effectively than naive controls. Surprisingly, however, this was not associated with accelerated removal of pRBCs from circulation. Instead, transfused pRBCs remained in circulation longer in acutely infected mice. Flow cytometric assessment and mathematical modeling of intraerythrocytic parasite development revealed an unexpected and substantial slowing of parasite maturation in acutely infected mice, extending the life cycle from 24 h to 40 h. Importantly, impaired parasite maturation was the major contributor to control of parasite growth in acutely infected mice. Moreover, by performing the same experiments in rag1 −/− mice, which lack T and B cells and mount weak inflammatory responses, we revealed that impaired parasite maturation is largely dependent upon the host response to infection. Thus, impairment of parasite maturation represents a host-mediated, immune system-dependent mechanism for limiting parasite population growth during the early stages of an acute blood-stage Plasmodium infection. malaria | clearance | mathematical modelling | Plasmodium berghei ANKA | parasite maturation

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“…The importance of these tissues is further underlined by their role in SIV and/or P. fragile infection. The spleen serves as the primary site for the clearance of parasiteinfected red blood cells (39,40), and lymphadenopathy is a common clinical feature in HIV/SIV infection.…”

Section: Distinct Tlr Responses Of Peripheral Blood MDC and Monocytesmentioning

confidence: 99%

Immune Activation and Regulation in Simian Immunodeficiency Virus-Plasmodium fragile-Coinfected Rhesus Macaques

Trott

Richardson

Hudgens

et al. 2013

J Virol

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The role of the spleen in malaria

Cited by 182 publications

References 101 publications

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Host-mediated impairment of parasite maturation during blood-stage Plasmodium infection

Immune Activation and Regulation in Simian Immunodeficiency Virus-Plasmodium fragile-Coinfected Rhesus Macaques

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