Bone Marrow Is a Major Parasite Reservoir in Plasmodium vivax Infection.

Autor:	Obaldia N 3rd; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.; Tropical Medicine Research, Panama City, Panama.; Instituto Conmemorativo Gorgas de Estudios de la Salud, Panama City, Panama., Meibalan E; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.; Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA., Sa JM; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA., Ma S; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA., Clark MA; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA., Mejia P; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA., Moraes Barros RR; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA., Otero W; Tropical Medicine Research, Panama City, Panama.; Instituto Conmemorativo Gorgas de Estudios de la Salud, Panama City, Panama., Ferreira MU; Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil., Mitchell JR; Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, USA., Milner DA; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA., Huttenhower C; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA., Wirth DF; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA., Duraisingh MT; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA., Wellems TE; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA., Marti M; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA matthias.marti@glasgow.ac.uk.; Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow, United Kingdom.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2018 May 08; Vol. 9 (3). Date of Electronic Publication: 2018 May 08.
DOI:	10.1128/mBio.00625-18
Abstrakt:	Plasmodium vivax causes heavy burdens of disease across malarious regions worldwide. Mature P. vivax asexual and transmissive gametocyte stages occur in the blood circulation, and it is often assumed that accumulation/sequestration in tissues is not an important phase in their development. Here, we present a systematic study of P. vivax stage distributions in infected tissues of nonhuman primate (NHP) malaria models as well as in blood from human infections. In a comparative analysis of the transcriptomes of P. vivax and Plasmodium falciparum blood-stage parasites, we found a conserved cascade of stage-specific gene expression despite the greatly different gametocyte maturity times of these two species. Using this knowledge, we validated a set of conserved asexual- and gametocyte-stage markers both by quantitative real-time PCR and by antibody assays of peripheral blood samples from infected patients and NHP ( Aotus sp.). Histological analyses of P. vivax parasites in organs of 13 infected NHP ( Aotus and Saimiri species) demonstrated a major fraction of immature gametocytes in the parenchyma of the bone marrow, while asexual schizont forms were enriched to a somewhat lesser extent in this region of the bone marrow as well as in sinusoids of the liver. These findings suggest that the bone marrow is an important reservoir for gametocyte development and proliferation of malaria parasites. IMPORTANCE Plasmodium vivax malaria continues to cause major public health burdens worldwide. Yet, significant knowledge gaps in the basic biology and epidemiology of P. vivax malaria remain, largely due to limited available tools for research and diagnostics. Here, we present a systematic examination of tissue sequestration during P. vivax infection. Studies of nonhuman primates and malaria patients revealed enrichment of developing sexual stages (gametocytes) and mature replicative stages (schizonts) in the bone marrow and liver, relative to those present in peripheral blood. Identification of the bone marrow as a major P. vivax tissue reservoir has important implications for parasite diagnosis and treatment. (Copyright © 2018 Obaldia et al.)
Databáze:	MEDLINE
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