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: liliana.mancio@inserm.fr.
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.
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Department of Chemistry, MIT, Cambridge, MA 02139, USA.
David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; BioMicro Center, MIT, Cambridge, MA 02139, USA.
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.
Mahidol Vivax Research Unit, Faculty of Tropical Medicine Mahidol University, Bangkok 10400, Thailand.
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: shalek@mit.edu.
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: sbhatia@mit.edu.
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.
