Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria.
The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms.
Malaria Immunology laboratory, Francis Crick Institute, 1 Midland Road, NW1 1AT London, United Kingdom.
Jing-Wen
JW
Lin
Malaria Immunology laboratory, Francis Crick Institute, 1 Midland Road, NW1 1AT London, United Kingdom.
Jan
J
Sodenkamp
Malaria Immunology laboratory, Francis Crick Institute, 1 Midland Road, NW1 1AT London, United Kingdom.
Deirdre
D
Cunningham
Malaria Immunology laboratory, Francis Crick Institute, 1 Midland Road, NW1 1AT London, United Kingdom.
Katrien
K
Deroost
Malaria Immunology laboratory, Francis Crick Institute, 1 Midland Road, NW1 1AT London, United Kingdom.
Tshibuayi Christine
TC
Tshitenge
Malaria Immunology laboratory, Francis Crick Institute, 1 Midland Road, NW1 1AT London, United Kingdom.
Sarah
S
McLaughlin
Malaria Immunology laboratory, Francis Crick Institute, 1 Midland Road, NW1 1AT London, United Kingdom.
Tracey J
TJ
Lamb
Experimental Histopathology, Francis Crick Institute, 1 Midland Road, NW1 1AT London, United Kingdom.
Bradley
B
Spencer-Dene
Malaria Immunology laboratory, Francis Crick Institute, 1 Midland Road, NW1 1AT London, United Kingdom.
Caroline
C
Hosking
Leiden Malaria Research Group, Leiden University Medical Center, Department of Parasitology, 2333 ZA Leiden, The Netherlands.
Jai
J
Ramesar
Leiden Malaria Research Group, Leiden University Medical Center, Department of Parasitology, 2333 ZA Leiden, The Netherlands.
Chris J
CJ
Janse
Immunoregulation and Infection laboratory, The Francis Crick Institute, NW1 1AT, London, United Kingdom.
Christine
C
Graham
Immunoregulation and Infection laboratory, The Francis Crick Institute, NW1 1AT, London, United Kingdom.
Anne
A
O'Garra
Malaria Immunology laboratory, Francis Crick Institute, 1 Midland Road, NW1 1AT London, United Kingdom.
Jean
J
Langhorne
D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000469:parasitology; D020869:Gene Expression Profiling; D006790:Host-Parasite Interactions / Q000235:genetics*; D008018:Life Cycle Stages; D008288:Malaria / Q000097:blood / Q000235:genetics* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009928:Organ Specificity / Q000235:genetics; D010961:Plasmodium / Q000502:physiology*; D016788:Plasmodium chabaudi / Q000502:physiology; D010974:Platelet Aggregation; D059467:Transcriptome; D014774:Virulence