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Th1 Cytokines Are Essential for Placental Immunity to Listeria monocytogenes

Author:
Barber, Ellen M., Fazzari, Melissa, Pollard, Jeffrey W.
Source:
Infection and immunity 2005 v.73 no.10 pp. 6322-6331
ISSN:
0019-9567
Subject:
Listeria monocytogenes, T-lymphocytes, allografting, bacteria, cytotoxicity, fetal death, fetus, genes, immune response, interferon-gamma, mice, mutation, neutrophils, pathogens, placenta, pregnancy, tumor necrosis factor-alpha
Abstract:
The fetal allograft poses an immunological challenge: how is it protected while immunity to pathogens, particularly those that replicate in the placenta, is maintained? Several theories have been proposed to explain this fetal protection, including a pregnancy-based bias towards a Th2 rather than Th1 cytokine profile in order to avoid generating cytotoxic T cells that could threaten the fetus. Listeria monocytogenes preferentially replicates in the placenta and systemically requires a Th1 response for sterile eradication. In the placenta, the Th1 cytokines tumor necrosis factor alpha (TNF-[alpha]) and gamma interferon (IFN-[gamma]) are also synthesized in response to this pathogen, without fetal loss. Here we show, by using mice homozygous for null mutations in either the cytokine or cytokine receptor genes, a requirement for both TNF-[alpha] and IFN-[gamma] signaling for an effective placental immune response to L. monocytogenes. However, T cells were not recruited to the placenta. Genetic studies in which the fetal component of the placenta was genetically different from the mother indicated that both the production of and response to these cytokines were maternal. Despite the requirement for these cytokines, the early recruitment of neutrophils to the placenta was normal. Consequently, the bacterium appeared to be delayed in its colonization of this organ and did not fully gain hold until 72 h postinfection. These data show a requirement for Th1 cytokines during pregnancy for effective immunity and indicate that a bias away from Th1 cytokine synthesis is not a necessary prerequisite of pregnancy.
Agid:
266782