Host response to malaria during pregnancy: placental monocyte recruitment is associated with elevated beta chemokine expression.
Malaria during pregnancy is associated with poor birth outcomes, particularly low birth weight. Recently, monocyte infiltration into the placental intervillous space has been identified as a key risk factor for low birth weight. However, the malaria-induced chemokines involved in recruiting and activating placental monocytes have not been identified. In this study, we determined which chemokines are elevated during placental malaria infection and the association between chemokine expression and placental monocyte infiltration. Placental malaria infection was associated with elevations in mRNA expression of three beta chemokines, macrophage-inflammatory protein 1 (MIP-1) alpha (CCL3), monocyte chemoattractant protein 1 (MCP-1; CCL2), and I-309 (CCL1), and one alpha chemokine, IL-8 (CXCL8); all correlated with monocyte density in the placental intervillous space. Placental plasma concentrations of MIP-1 alpha and IL-8 were increased in women with placental malaria and were associated with placental monocyte infiltration. By immunohistochemistry, we localized placental chemokine production in malaria-infected placentas: some but not all hemozoin-laden maternal macrophages produced MIP-1 beta and MCP-1, and fetal stromal cells produced MCP-1. In sum, local placental production of chemokines is increased in malaria, and may be an important trigger for monocyte accumulation in the placenta.
Abrams
Elizabeth T
ET
Department of Anthropology, University of Michigan, Ann Arbor, MI 48104, USA.
Brown
Heidi
H
Chensue
Stephen W
SW
Turner
Gareth D H
GD
Tadesse
Eyob
E
Lema
Valentino M
VM
Molyneux
Malcolm E
ME
Rochford
Rosemary
R
Meshnick
Steven R
SR
Rogerson
Stephen J
SJ
D001724:Birth Weight / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D054402:Chemokine CCL1; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D010920:Placenta / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis
C065971:CCL1 protein, human; D054402:Chemokine CCL1; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger