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Monocyte malaria

Vikas Shrivastava, Sohaib Ahmad, Garima Mittal, Vibha Gupta, Nadia Shirazi, Varun Kalra
Background: In this follow-up study, we aimed to establish the cut-off values of the volume, conductivity and scatter (VCS) parameters of leucocytes that significantly differ in dengue fever, malaria, scrub typhus and enteric fever, as described in our pilot study. Methods: A prospective observational case-control study was undertaken on patients with an established diagnosis of acute malaria (n=476), dengue fever (n=927), scrub typhus (n=425), bacterial sepsis (n=1598) or enteric fever (n=885) and the haematological and VCS data obtained by the Coulter LH 750 analyser were compared with controls...
March 2, 2018: Transactions of the Royal Society of Tropical Medicine and Hygiene
Sitang Maknitikul, Natthanej Luplertlop, Urai Chaisri, Yaowapa Maneerat, Sumate Ampawong
Plasmodium falciparum, the most virulent malaria parasite species, causes severe symptoms especially acute lung injury (ALI), of which characterized by alveolar epithelium and endothelium destruction and accelerated to blood-gas-barrier breakdown. Parasitized erythrocytes, endothelial cells, monocytes, and cytokines are all involved in this mechanism, but hemozoin (HZ), the parasitic waste from heme detoxification, also mainly contributes. In addition, it is not clear why type II pneumocyte proliferation, alveolar restorative stage, is rare in malaria-associated ALI...
January 1, 2018: Experimental Biology and Medicine
Mirja Hommel, Jo-Anne Chan, Alexandra J Umbers, Christine Langer, Stephen J Rogerson, Joseph D Smith, James G Beeson
BACKGROUND: Malaria in pregnancy is a major cause of poor maternal and infant health, and is associated with the sequestration of P. falciparum-infected erythrocytes (IE) in the placenta. The leading vaccine candidate for pregnancy malaria, VAR2CSA, has been shown to induce antibodies that inhibit IE adhesion to the placental receptor chondroitin sulfate A (CSA), potentially preventing placental infection. However, the ability of vaccination-induced antibodies to promote opsonic phagocytosis is not well defined, but likely to be an important component of protective immunity...
January 29, 2018: Parasites & Vectors
Natália G Sampaio, Samantha J Emery, Alexandra L Garnham, Qiao Y Tan, Xavier Sisquella, Matthew A Pimentel, Aaron R Jex, Neta Regev-Rudzki, Louis Schofield, Emily M Eriksson
Pathogens can release extracellular vesicles (EVs) for cell-cell communication and host modulation. EVs from Plasmodium falciparum, the deadliest malaria parasite species, can transfer drug resistance genes between parasites. EVs from late-stage parasite-infected RBC (iRBC-EVs) are immunostimulatory and affect endothelial cell permeability, but little is known about EVs from early stage iRBC. We detected the parasite virulence factor PfEMP1, which is responsible for iRBC adherence and a major contributor to disease severity, in EVs, only up to 12-hr post-RBC invasion...
January 18, 2018: Cellular Microbiology
Kylie R James, Megan S F Soon, Ismail Sebina, Daniel Fernandez-Ruiz, Gayle Davey, Urijah N Liligeto, Arya Sheela Nair, Lily G Fogg, Chelsea L Edwards, Shannon E Best, Lianne I M Lansink, Kate Schroder, Jane A C Wilson, Rebecca Austin, Andreas Suhrbier, Steven W Lane, Geoffrey R Hill, Christian R Engwerda, William R Heath, Ashraful Haque
Differentiation of CD4+ Th cells is critical for immunity to malaria. Several innate immune signaling pathways have been implicated in the detection of blood-stage Plasmodium parasites, yet their influence over Th cell immunity remains unclear. In this study, we used Plasmodium-reactive TCR transgenic CD4+ T cells, termed PbTII cells, during nonlethal P. chabaudi chabaudi AS and P. yoelii 17XNL infection in mice, to examine Th cell development in vivo. We found no role for caspase1/11, stimulator of IFN genes, or mitochondrial antiviral-signaling protein, and only modest roles for MyD88 and TRIF-dependent signaling in controlling PbTII cell expansion...
January 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Xavier Sisquella, Yifat Ofir-Birin, Matthew A Pimentel, Lesley Cheng, Paula Abou Karam, Natália G Sampaio, Jocelyn Sietsma Penington, Dympna Connolly, Tal Giladi, Benjamin J Scicluna, Robyn A Sharples, Andreea Waltmann, Dror Avni, Eli Schwartz, Louis Schofield, Ziv Porat, Diana S Hansen, Anthony T Papenfuss, Emily M Eriksson, Motti Gerlic, Andrew F Hill, Andrew G Bowie, Neta Regev-Rudzki
STING is an innate immune cytosolic adaptor for DNA sensors that engage malaria parasite (Plasmodium falciparum) or other pathogen DNA. As P. falciparum infects red blood cells and not leukocytes, how parasite DNA reaches such host cytosolic DNA sensors in immune cells is unclear. Here we show that malaria parasites inside red blood cells can engage host cytosolic innate immune cell receptors from a distance by secreting extracellular vesicles (EV) containing parasitic small RNA and genomic DNA. Upon internalization of DNA-harboring EVs by human monocytes, P...
December 7, 2017: Nature Communications
Carolina Gallego-Marin, Jacob E Schrum, Warrison A Andrade, Scott A Shaffer, Lina F Giraldo, Alvaro M Lasso, Evelyn A Kurt-Jones, Katherine A Fitzgerald, Douglas T Golenbock
Innate immune receptors have a key role in the sensing of malaria and initiating immune responses. As a consequence of infection, systemic inflammation emerges and is directly related to signs and symptoms during acute disease. We have previously reported that plasmodial DNA is the primary driver of systemic inflammation in malaria, both within the phagolysosome and in the cytosol of effector cells. In this article, we demonstrate that Plasmodium falciparum genomic DNA delivered to the cytosol of human monocytes binds and activates cyclic GMP-AMP synthase (cGAS)...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Yan Tang, Chester J Joyner, Monica Cabrera-Mora, Celia L Saney, Stacey A Lapp, Mustafa V Nural, Suman B Pakala, Jeremy D DeBarry, Stephanie Soderberg, Jessica C Kissinger, Tracey J Lamb, Mary R Galinski, Mark P Styczynski
After publication of the article [1], it was brought to our attention that several symbols were missing from Fig. 1, including some cited in the figure's key. The correct version of the figure is shown below and has now been updated in the original article.
December 4, 2017: Malaria Journal
Marlies E van Wolfswinkel, Marijke C C Langenberg, Linda J Wammes, Robert W Sauerwein, Rob Koelewijn, Cornelus C Hermsen, Jaap J van Hellemond, Perry J van Genderen
BACKGROUND: Both in endemic countries and in imported malaria, changes in total and differential leukocyte count during Plasmodium falciparum infection have been described. To study the exact dynamics of differential leukocyte counts and their ratios, they were monitored in a group of healthy non-immune volunteers in two separate Controlled Human Malaria Infection (CHMI) studies. METHODS: In two CHMI trials, CHMI-a and CHMI-b, 15 and 24 healthy malaria-naïve volunteers, respectively, were exposed to bites of infected mosquitoes, using the P...
November 10, 2017: Malaria Journal
Cesar Terrazas, Sanjay Varikuti, Steve Oghumu, Heidi M Steinkamp, Nurittin Ardic, Jennifer Kimble, Hira Nakhasi, Abhay R Satoskar
Ly6C(hi) inflammatory monocytes (iMO) are critical for host defense against toxoplasmosis and malaria but their role in leishmaniasis is unclear. In this study, we report a detrimental role of Ly6C(hi) iMOs in visceral leishmaniasis (VL) caused by Leishmania donovani. We demonstrate that Ly6C(hi) iMOs are continuously recruited into the spleen and liver during L. donovani infection and they are preferential targets for the parasite. Using microarray-based gene expression profiling, we show that Ly6C(hi) iMOs isolated from the infected liver and spleen have distinct phenotypic and activation profiles...
October 31, 2017: Scientific Reports
Elvin Lufele, Alexandra Umbers, Jaume Ordi, Maria Ome-Kaius, Regina Wangnapi, Holger Unger, Nandao Tarongka, Peter Siba, Ivo Mueller, Leanne Robinson, Stephen Rogerson
BACKGROUND: Plasmodium falciparum in pregnancy results in substantial poor health outcomes for both mother and child, particularly in young, primigravid mothers who are at greatest risk of placental malaria (PM) infection. Complications of PM include maternal anaemia, low birth weight and preterm delivery, which contribute to maternal and infant morbidity and mortality in coastal Papua New Guinea (PNG). METHODS: Placental biopsies were examined from 1451 pregnant women who were enrolled in a malaria prevention study at 14-26 weeks gestation...
October 24, 2017: Malaria Journal
Natália Guimarães Sampaio, Emily Marie Eriksson, Louis Schofield
Immunity to Plasmodium falciparum malaria is slow to develop, and it is often asserted that malaria suppresses host immunity, although this is poorly understood and the molecular basis for such activity remains unknown. P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) is a virulence factor that plays a key role in parasite-host interactions. We investigated the immunosuppressive effect of PfEMP1 on monocytes/macrophages, which are central to the anti-parasitic innate response. RAW macrophages and human primary monocytes were stimulated with wild-type 3D7 or CS2 parasites or transgenic PfEMP1-null parasites...
October 16, 2017: Infection and Immunity
Janaiara A Cunha, Leonardo J M Carvalho, Cesare Bianco-Junior, Márcia C R Andrade, Lilian R Pratt-Riccio, Evelyn K P Riccio, Marcelo Pelajo-Machado, Igor J da Silva, Pierre Druilhe, Cláudio Tadeu Daniel-Ribeiro
A major constraint in the study of Plasmodium falciparum malaria, including vaccine development, lies on the parasite's strict human host specificity and therefore the shortage of animal experimental models able to harbor human plasmodia. The best experimental models are neo-tropical primates of the genus Saimiri and Aotus, but they require splenectomy to reduce innate defenses for achieving high and consistent parasitemias, an important limitation. Clodronate-liposomes (CL) have been successfully used to deplete monocytes/macrophages in several experimental models...
2017: Frontiers in Cellular and Infection Microbiology
Yan Tang, Chester J Joyner, Monica Cabrera-Mora, Celia L Saney, Stacey A Lapp, Mustafa V Nural, Suman B Pakala, Jeremy D DeBarry, Stephanie Soderberg, Jessica C Kissinger, Tracey J Lamb, Mary R Galinski, Mark P Styczynski
BACKGROUND: Mild to severe anaemia is a common complication of malaria that is caused in part by insufficient erythropoiesis in the bone marrow. This study used systems biology to evaluate the transcriptional and alterations in cell populations in the bone marrow during Plasmodium cynomolgi infection of rhesus macaques (a model of Plasmodium vivax malaria) that may affect erythropoiesis. RESULTS: An appropriate erythropoietic response did not occur to compensate for anaemia during acute cynomolgi malaria despite an increase in erythropoietin levels...
September 22, 2017: Malaria Journal
Katherine R Dobbs, Paula Embury, John Vulule, Peter S Odada, Bruce A Rosa, Makedonka Mitreva, James W Kazura, Arlene E Dent
BACKGROUND: Inflammation and monocytes are thought to be important to human malaria pathogenesis. However, the relationship of inflammation and various monocyte functions to acute malaria, recovery from acute malaria, and asymptomatic parasitemia in endemic populations is poorly understood. METHODS: We evaluated plasma cytokine levels, monocyte subsets, monocyte functional responses, and monocyte inflammatory transcriptional profiles of 1- to 10-year-old Kenyan children at the time of presentation with acute uncomplicated malaria and at recovery 6 weeks later; these results were compared with analogous data from asymptomatic children and adults in the same community...
September 21, 2017: JCI Insight
Jaclyn E Quin, Ioana Bujila, Mariama Chérif, Guillaume S Sanou, Ying Qu, Manijeh Vafa Homann, Anna Rolicka, Sodiomon B Sirima, Mary A O'Connell, Andreas Lennartsson, Marita Troye-Blomberg, Issa Nebie, Ann-Kristin Östlund Farrants
The Fulani ethnic group has relatively better protection from Plasmodium falciparum malaria, as reflected by fewer symptomatic cases of malaria, lower infection rates, and lower parasite densities compared to sympatric ethnic groups. However, the basis for this lower susceptibility to malaria by the Fulani is unknown. The incidence of classic malaria resistance genes are lower in the Fulani than in other sympatric ethnic populations, and targeted SNP analyses of other candidate genes involved in the immune response to malaria have not been able to account for the observed difference in the Fulani susceptibility to P...
September 19, 2017: ELife
Anja Jäschke, Boubacar Coulibaly, Edmond J Remarque, Hermann Bujard, Christian Epp
Naturally acquired immunity against malaria is largely mediated by serum antibodies controlling levels of blood-stage parasites. A limited understanding of the antigenic targets and functional mechanisms of protective antibodies has hampered the development of efficient malaria vaccines. Besides directly inhibiting the growth of Plasmodium parasites, antibodies can opsonize merozoites and recruit immune effector cells such as monocytes and neutrophils. Antibodies against the vaccine candidate merozoite surface protein 1 (MSP-1) are acquired during natural infections and have been associated with protection against malaria in several epidemiological studies...
November 2017: Clinical and Vaccine Immunology: CVI
Adriana A Marin Rodriguez, Leonardo J M Carvalho, Emilia A Kimura, Alejandro M Katzin
The development of new drugs is one of the strategies to control malaria. Isoprenoid biosynthesis in Plasmodium falciparum is an essential pathway for parasite survival, and therefore a potential target for new antimalarial drugs. Indeed, plant-derived secondary metabolites such as terpenes exhibit antimalarial activity in vitro by inhibiting isoprenoid biosynthesis in P. falciparum. In this study, the in vitro antiplasmodial activity of perillyl alcohol (POH) was evaluated, along with its in vitro toxicity and its effect on the isoprenylation process...
August 23, 2017: International Journal of Antimicrobial Agents
Jo-Anne Chan, Danielle I Stanisic, Michael F Duffy, Leanne J Robinson, Enmoore Lin, James W Kazura, Christopher L King, Peter M Siba, Freya Ji Fowkes, Ivo Mueller, James G Beeson
Acquired antibodies play an important role in immunity to P. falciparum malaria and are typically directed towards surface antigens expressed by merozoites and infected erythrocytes (IEs). The importance of specific IE surface antigens as immune targets remains unclear. We evaluated antibodies and protective associations in two cohorts of children in Papua New Guinea. We used genetically-modified P. falciparum to evaluate the importance of PfEMP1 and a P. falciparum isolate with a virulent phenotype. Our findings suggested that PfEMP1 was the dominant target of antibodies to the IE surface, including functional antibodies that promoted opsonic phagocytosis by monocytes...
December 2017: European Journal of Immunology
D Bujarbaruah, M P Kalita, V Baruah, T K Basumatary, S Hazarika, R H Begum, S Medhi, S Bose
The study explored the role of differential RANTES concentrations, its receptor CCR5 expression and resulting immunomodulation in the pathogenesis and/or recovery from falciparum malaria. The study population included cases of uncomplicated malaria (UC-M, N=128, enrolled on follow-up basis), severe malaria (SM, N=25), and healthy controls (N=112). Serum RANTES and TNF-α levels were evaluated by ELISA. Monocyte levels and activation profile were studied by flow cytometry. Differential mRNA expression profile was studied by real-time PCR...
September 2017: Parasite Immunology
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