A single-cell liver atlas of Plasmodium vivax infection

Liliana Mancio-Silva; Nil Gural; Eliana Real; Marc H Wadsworth 2nd; Vincent L Butty; Sandra March; Niketa Nerurkar; Travis K Hughes; Wanlapa Roobsoong; Heather E Fleming; Charlie A Whittaker; Stuart S Levine; Jetsumon Sattabongkot; Alex K Shalek; Sangeeta N Bhatia

doi:10.1016/j.chom.2022.03.034

A single-cell liver atlas of Plasmodium vivax infection

Cell Host Microbe. 2022 Jul 13;30(7):1048-1060.e5. doi: 10.1016/j.chom.2022.03.034. Epub 2022 Apr 19.

Authors

Affiliations

¹ Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; Institut Pasteur, Université Paris Cité, Inserm U1201, CNRS EMR9195, Unité de Biologie des Interactions Hôte-Parasite, 75015 Paris, France. Electronic address: [email protected].
² Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA.
³ Institut Pasteur, Université Paris Cité, Inserm U1201, CNRS EMR9195, Unité de Biologie des Interactions Hôte-Parasite, 75015 Paris, France.
⁴ Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Department of Chemistry, MIT, Cambridge, MA 02139, USA.
⁵ David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; BioMicro Center, MIT, Cambridge, MA 02139, USA.
⁶ Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
⁷ Mahidol Vivax Research Unit, Faculty of Tropical Medicine Mahidol University, Bangkok 10400, Thailand.
⁸ Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; Department of Chemistry, MIT, Cambridge, MA 02139, USA; Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: [email protected].
⁹ Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; The Wyss Institute for Biologically Inspired Engineering Harvard University Boston, MA 02215, USA. Electronic address: [email protected].

PMID: 35443155
DOI: 10.1016/j.chom.2022.03.034

Abstract

Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years and reactivate to cause recurrent blood-stage infection. Although they are an important target for malaria eradication, little is known about the molecular features of replicative and non-replicative intracellular liver-stage parasites and their host cell dependence. Here, we leverage a bioengineered human microliver platform to culture patient-derived P. vivax parasites for transcriptional profiling. Coupling enrichment strategies with bulk and single-cell analyses, we capture both parasite and host transcripts in individual hepatocytes throughout the course of infection. We define host- and state-dependent transcriptional signatures and identify unappreciated populations of replicative and non-replicative parasites that share features with sexual transmissive forms. We find that infection suppresses the transcription of key hepatocyte function genes and elicits an anti-parasite innate immune response. Our work provides a foundation for understanding host-parasite interactions and reveals insights into the biology of P. vivax dormancy and transmission.

Keywords: MPCC; Plasmodium vivax; Seq-Well; dormancy; host-parasite interactions; hypnozoites; liver stage; single-cell; transcriptomics; transmission.

MeSH terms

Hepatocytes / parasitology
Humans
Liver / parasitology
Malaria* / parasitology
Malaria, Vivax* / parasitology
Plasmodium vivax / genetics