The trophoblast is a component of the innate immune system during pregnancy.
Systemic infection with Listeria monocytogenes, a Gram-positive intracellular bacterium, has been used extensively to analyze the innate immune response. Macrophages are central to this response, acting as both the host for and principal defense against this bacterium. During pregnancy L. monocytogenes has a predilection for replication at the maternal-placental interface and consequently is an important cause of fetal morbidity and mortality. However, macrophages are mostly excluded from the murine placenta with neutrophils acting as the main immune effector cell against this bacterium. Colony stimulating factor (CSF)-1, a macrophage growth factor, is synthesized in high concentrations by the uterine epithelium during pregnancy, where it is targeted to trophoblast bearing CSF-1-receptors. To define the involvement of CSF-1 in placental immunity, we infected pregnant mice either homozygous or heterozygous for an inactivating recessive mutation in the gene for CSF-1 (osteopetrotic; Csfmop) with L. monocytogenes. CSF-1 was required to recruit neutrophils to the site of listerial infection in the decidua basalis, and infection by Listeria remained unrestrained in its absence. CSF-1 acted by inducing the trophoblast to synthesize the neutrophil chemoattractants (KC) and macrophage inflammatory protein (MIP)-2. Thus, during pregnancy, trophoblast responsive to CSF-1 acts to organize the maternal immune response to bacterial infection at the utero-placental interface. This previously unknown function indicates that the trophoblast acts as a pregnancy-specific component of the innate immune system.
Guleria
I
I
Departments of Developmental and Molecular Biology and Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, New York 10461, USA.
Pollard
J W
JW
D000818:Animals; D018925:Chemokines / Q000032:analysis; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D005260:Female; D008088:Listeriosis / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010920:Placenta / Q000276:immunology* / Q000382:microbiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D018417:Th1 Cells; D018418:Th2 Cells; D014327:Trophoblasts / Q000276:immunology*
D018925:Chemokines; D016207:Cytokines; D016173:Macrophage Colony-Stimulating Factor