Abstract
Systemic infection with Listeria monocytogenes, a Gram-positive intracellular bacterium, has been used extensively to analyze the innate immune response1,2. 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 mortality3,4. However, macrophages are mostly excluded from the murine placenta with neutrophils acting as the main immune effector cell against this bacterium3,5,6. 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-receptors7,8. 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. monocytogenes9. 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.
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Acknowledgements
We thank P. Cohen and M. Scharff for critical comments on the manuscript and X. Chen and J. Lee for technical support. This work was supported by National Institutes of Health grant HD30280 and by the Albert Einstein Comprehensive Cancer Center grant, P30-CA13330. J.W.P. is the Betty E Feinberg Senior Faculty Scholar in Cancer Research.
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Guleria, I., Pollard, J. The trophoblast is a component of the innate immune system during pregnancy . Nat Med 6, 589–593 (2000). https://doi.org/10.1038/75074
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DOI: https://doi.org/10.1038/75074
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