Peripheral blood mononuclear cells derived from grand multigravidae display a distinct cytokine profile in response to P. falciparum infected erythrocytes.
Immunopathology of placental malaria is most significant in women in their first pregnancy especially in endemic areas, due to a lack of protective immunity to Plasmodium falciparum, which is acquired in successive pregnancies. In some studies (but not all), grand multigravidae (defined as 5 or more pregnancies, G5-7) are more susceptible to poor birth outcomes associated with malaria compared to earlier gravidities. By comparing peripheral cellular responses in primigravidae (G1), women in their second to fourth pregnancy (G2-4) and grand multigravidae we sought to identify key components of the dysregulated immune response. PBMC were exposed to CS2-infected erythrocytes (IE) opsonised with autologous plasma or unopsonised IE, and cytokine and chemokine secretion was measured. Higher levels of opsonising antibody were present in plasma derived from multigravid compared to primigravid women. Significant differences in the levels of cytokines and chemokines secreted in response to IE were observed. Less IL-10, IL-1β, IL-6 and TNF but more CXCL8, CCL8, IFNγ and CXCL10 were detected in G5-7 compared to G2-4 women. Our study provides fresh insight into the modulation of peripheral blood cell function and effects on the balance between host protection and immunopathology during placental malaria infection.
Department of Medicine (RMH), University of Melbourne, Post Office Royal Melbourne Hospital, Melbourne, Victoria, Australia ; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria, Australia.
Louise E
LE
Ludlow
Department of Medicine (RMH), University of Melbourne, Post Office Royal Melbourne Hospital, Melbourne, Victoria, Australia ; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria, Australia.
Wina
W
Hasang
Department of Medicine (RMH), University of Melbourne, Post Office Royal Melbourne Hospital, Melbourne, Victoria, Australia ; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria, Australia ; Papua New Guinea Institute of Medical Research, Vector Borne Disease Unit, Madang, PNG.
Alexandra J
AJ
Umbers
Department of Medicine (RMH), University of Melbourne, Post Office Royal Melbourne Hospital, Melbourne, Victoria, Australia ; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria, Australia.
Emily K
EK
Forbes
Papua New Guinea Institute of Medical Research, Vector Borne Disease Unit, Madang, PNG.
Maria
M
Ome
Department of Medicine (RMH), University of Melbourne, Post Office Royal Melbourne Hospital, Melbourne, Victoria, Australia ; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria, Australia ; Papua New Guinea Institute of Medical Research, Vector Borne Disease Unit, Madang, PNG.
Holger W
HW
Unger
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia ; Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
Ivo
I
Mueller
Papua New Guinea Institute of Medical Research, Vector Borne Disease Unit, Madang, PNG.
Peter M
PM
Siba
Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia ; Department of Infectious Diseases, Monash University, Victoria, Australia ; Department of Immunology, Monash University, Victoria, Australia.
Anthony
A
Jaworowski
Department of Medicine (RMH), University of Melbourne, Post Office Royal Melbourne Hospital, Melbourne, Victoria, Australia ; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria, Australia.
Stephen J
SJ
Rogerson
D000328:Adult; D000906:Antibodies / Q000097:blood; D002460:Cell Line; D016207:Cytokines / Q000097:blood*; D004198:Disease Susceptibility; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D020073:Gravidity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D016778:Malaria, Falciparum / Q000097:blood* / Q000276:immunology* / Q000469:parasitology; D009895:Opsonin Proteins / Q000097:blood; D010920:Placenta / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic; D055815:Young Adult
D000906:Antibodies; D016207:Cytokines; D009895:Opsonin Proteins