Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system

Pierre Yves Mantel; Anh N. Hoang; Ilana Goldowitz; Daria Potashnikova; Bashar Hamza; Ivan Vorobjev; Ionita Ghiran; Mehmet Toner; Daniel Irimia; Alexander R. Ivanov; Natasha Barteneva; Matthias Marti

doi:10.1016/j.chom.2013.04.009

Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system

Pierre Yves Mantel
, Anh N. Hoang
, Ilana Goldowitz
, Daria Potashnikova
, Bashar Hamza
, Ivan Vorobjev
, Ionita Ghiran
, Mehmet Toner
, Daniel Irimia
, Alexander R. Ivanov
, Natasha Barteneva
, Matthias Marti

Harvard University
Lomonosov Moscow State University
Northeastern University

Research output: Contribution to journal › Article › peer-review

350 Citations (Scopus)

Abstract

Humans and mice infected with different Plasmodium strains are known to produce microvesicles derived from the infected red blood cells (RBCs), denoted RMVs. Studies in mice have shown that RMVs are elevated during infection and have proinflammatory activity. Here we present a detailed characterization of RMV composition and function in the human malaria parasite Plasmodium falciparum. Proteomics profiling revealed the enrichment of multiple host and parasite proteins, in particular of parasite antigens associated with host cell membranes and proteins involved in parasite invasion into RBCs. RMVs are quantitatively released during the asexual parasite cycle prior to parasite egress. RMVs demonstrate potent immunomodulatory properties on human primary macrophages and neutrophils. Additionally, RMVs are internalized by infected red blood cells and stimulate production of transmission stage parasites in a dose-dependent manner. Thus, RMVs mediate cellular communication within the parasite population and with the host innate immune system.

Original language	English
Pages (from-to)	521-534
Number of pages	14
Journal	Cell Host and Microbe
Volume	13
Issue number	5
DOIs	https://doi.org/10.1016/j.chom.2013.04.009
Publication status	Published - May 15 2013
Externally published	Yes

Funding

We acknowledge Maria Ericsson for expert technical support with electron microscopy, Dr. Xandra Breakefield for access to the NanoSight platform, and Drs. Barbara Burleigh and Barry Bloom for critical reading of the manuscript. Drs. Klaus Lingelbach (anti-Exp-1), Brian Cooke (anti-SBP1), Diane Taylor (anti-KAHRP), Robin Anders (anti-RESA and anti-AMA1), and Alan Cowman (anti-ATS 6H1, anti-EBA-175, and anti-EBA-181) are gratefully acknowledged for providing specific antisera to P. falciparum proteins. Anti-BIP has been provided by MR4 as MRA19. Thanks to Drs. Sarah Volkman for parasite strains Sen.T135.09 and Sen.T151.09, Joe Smith for parasite strains Pf2004 and Pf2006, and Manoj Duraisingh for the CDPK5-DD transgenic parasite line. We also acknowledge Dr. Pardis Sabeti for providing us with aliquots of serum samples derived from the Millennium Village Project and Dr. Barry Karger for his instrumental support. This work has been supported through a collaborative seed grant from Harvard Catalyst to M.M., N.A.B., and A.R.I., a Becton Dickinson Bioscience Immunology Award (M.M. and N.B.), Grand Challenges Exploration grant OPP1069401 from the Bill and Melinda Gates Foundation (D.I.), and a Novartis Foundation research fellowship to P.-Y.M.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

Access to Document

10.1016/j.chom.2013.04.009

Cite this

Mantel, P. Y., Hoang, A. N., Goldowitz, I., Potashnikova, D., Hamza, B., Vorobjev, I., Ghiran, I., Toner, M., Irimia, D., Ivanov, A. R., Barteneva, N., & Marti, M. (2013). Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system. Cell Host and Microbe, 13(5), 521-534. https://doi.org/10.1016/j.chom.2013.04.009

Mantel, PY, Hoang, AN, Goldowitz, I, Potashnikova, D, Hamza, B, Vorobjev, I, Ghiran, I, Toner, M, Irimia, D, Ivanov, AR, Barteneva, N & Marti, M 2013, 'Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system', Cell Host and Microbe, vol. 13, no. 5, pp. 521-534. https://doi.org/10.1016/j.chom.2013.04.009

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title = "Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system",

abstract = "Humans and mice infected with different Plasmodium strains are known to produce microvesicles derived from the infected red blood cells (RBCs), denoted RMVs. Studies in mice have shown that RMVs are elevated during infection and have proinflammatory activity. Here we present a detailed characterization of RMV composition and function in the human malaria parasite Plasmodium falciparum. Proteomics profiling revealed the enrichment of multiple host and parasite proteins, in particular of parasite antigens associated with host cell membranes and proteins involved in parasite invasion into RBCs. RMVs are quantitatively released during the asexual parasite cycle prior to parasite egress. RMVs demonstrate potent immunomodulatory properties on human primary macrophages and neutrophils. Additionally, RMVs are internalized by infected red blood cells and stimulate production of transmission stage parasites in a dose-dependent manner. Thus, RMVs mediate cellular communication within the parasite population and with the host innate immune system.",

author = "Mantel, \{Pierre Yves\} and Hoang, \{Anh N.\} and Ilana Goldowitz and Daria Potashnikova and Bashar Hamza and Ivan Vorobjev and Ionita Ghiran and Mehmet Toner and Daniel Irimia and Ivanov, \{Alexander R.\} and Natasha Barteneva and Matthias Marti",

note = "Funding Information: We acknowledge Maria Ericsson for expert technical support with electron microscopy, Dr. Xandra Breakefield for access to the NanoSight platform, and Drs. Barbara Burleigh and Barry Bloom for critical reading of the manuscript. Drs. Klaus Lingelbach (anti-Exp-1), Brian Cooke (anti-SBP1), Diane Taylor (anti-KAHRP), Robin Anders (anti-RESA and anti-AMA1), and Alan Cowman (anti-ATS 6H1, anti-EBA-175, and anti-EBA-181) are gratefully acknowledged for providing specific antisera to P. falciparum proteins. Anti-BIP has been provided by MR4 as MRA19. Thanks to Drs. Sarah Volkman for parasite strains Sen.T135.09 and Sen.T151.09, Joe Smith for parasite strains Pf2004 and Pf2006, and Manoj Duraisingh for the CDPK5-DD transgenic parasite line. We also acknowledge Dr. Pardis Sabeti for providing us with aliquots of serum samples derived from the Millennium Village Project and Dr. Barry Karger for his instrumental support. This work has been supported through a collaborative seed grant from Harvard Catalyst to M.M., N.A.B., and A.R.I., a Becton Dickinson Bioscience Immunology Award (M.M. and N.B.), Grand Challenges Exploration grant OPP1069401 from the Bill and Melinda Gates Foundation (D.I.), and a Novartis Foundation research fellowship to P.-Y.M. ",

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doi = "10.1016/j.chom.2013.04.009",

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AU - Mantel, Pierre Yves

AU - Hoang, Anh N.

AU - Goldowitz, Ilana

AU - Potashnikova, Daria

AU - Hamza, Bashar

AU - Vorobjev, Ivan

AU - Ghiran, Ionita

AU - Toner, Mehmet

AU - Irimia, Daniel

AU - Ivanov, Alexander R.

AU - Barteneva, Natasha

AU - Marti, Matthias

N1 - Funding Information: We acknowledge Maria Ericsson for expert technical support with electron microscopy, Dr. Xandra Breakefield for access to the NanoSight platform, and Drs. Barbara Burleigh and Barry Bloom for critical reading of the manuscript. Drs. Klaus Lingelbach (anti-Exp-1), Brian Cooke (anti-SBP1), Diane Taylor (anti-KAHRP), Robin Anders (anti-RESA and anti-AMA1), and Alan Cowman (anti-ATS 6H1, anti-EBA-175, and anti-EBA-181) are gratefully acknowledged for providing specific antisera to P. falciparum proteins. Anti-BIP has been provided by MR4 as MRA19. Thanks to Drs. Sarah Volkman for parasite strains Sen.T135.09 and Sen.T151.09, Joe Smith for parasite strains Pf2004 and Pf2006, and Manoj Duraisingh for the CDPK5-DD transgenic parasite line. We also acknowledge Dr. Pardis Sabeti for providing us with aliquots of serum samples derived from the Millennium Village Project and Dr. Barry Karger for his instrumental support. This work has been supported through a collaborative seed grant from Harvard Catalyst to M.M., N.A.B., and A.R.I., a Becton Dickinson Bioscience Immunology Award (M.M. and N.B.), Grand Challenges Exploration grant OPP1069401 from the Bill and Melinda Gates Foundation (D.I.), and a Novartis Foundation research fellowship to P.-Y.M.

PY - 2013/5/15

Y1 - 2013/5/15

N2 - Humans and mice infected with different Plasmodium strains are known to produce microvesicles derived from the infected red blood cells (RBCs), denoted RMVs. Studies in mice have shown that RMVs are elevated during infection and have proinflammatory activity. Here we present a detailed characterization of RMV composition and function in the human malaria parasite Plasmodium falciparum. Proteomics profiling revealed the enrichment of multiple host and parasite proteins, in particular of parasite antigens associated with host cell membranes and proteins involved in parasite invasion into RBCs. RMVs are quantitatively released during the asexual parasite cycle prior to parasite egress. RMVs demonstrate potent immunomodulatory properties on human primary macrophages and neutrophils. Additionally, RMVs are internalized by infected red blood cells and stimulate production of transmission stage parasites in a dose-dependent manner. Thus, RMVs mediate cellular communication within the parasite population and with the host innate immune system.

AB - Humans and mice infected with different Plasmodium strains are known to produce microvesicles derived from the infected red blood cells (RBCs), denoted RMVs. Studies in mice have shown that RMVs are elevated during infection and have proinflammatory activity. Here we present a detailed characterization of RMV composition and function in the human malaria parasite Plasmodium falciparum. Proteomics profiling revealed the enrichment of multiple host and parasite proteins, in particular of parasite antigens associated with host cell membranes and proteins involved in parasite invasion into RBCs. RMVs are quantitatively released during the asexual parasite cycle prior to parasite egress. RMVs demonstrate potent immunomodulatory properties on human primary macrophages and neutrophils. Additionally, RMVs are internalized by infected red blood cells and stimulate production of transmission stage parasites in a dose-dependent manner. Thus, RMVs mediate cellular communication within the parasite population and with the host innate immune system.

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Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system

Abstract

Funding

UN SDGs

ASJC Scopus subject areas

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