Bone Marrow Is a Major Parasite Reservoir in Plasmodium vivax Infection

mBio

Siyuan Ma¹  Curtis Huttenhower¹  James R. Mitchell²  Nicanor Obaldia³  Elamaran Meibalan³  Danny A. Milner³  Pedro Mejia³  Martha A. Clark³  Manoj T. Duraisingh³  Matthias Marti³  Dyann F. Wirth³  Marcelo U. Ferreira⁴  Roberto R. Moraes Barros⁵  Thomas E. Wellems⁵  Juliana M. Sa⁵  William Otero⁶ 

[1] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA;Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, USA;Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA;Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil;Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA;Tropical Medicine Research, Panama City, Panama;

关键词: Aotus;    real-time PCR;    Saimiri;    blood-stage parasites;    gametocytes;    immunohistochemistry;   

DOI  :  10.1128/mBio.00625-18

来源: DOAJ

【 摘 要 】

ABSTRACT 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.

【 授权许可】

Unknown