ovalbumin and Fetal-Death

Mammalian pregnancy requires protection against immunological rejection of the developing fetus bearing discordant paternal antigens. Immune evasion in this developmental context entails silenced expression of chemoattractant proteins (chemokines), thereby preventing harmful immune cells from penetrating the maternal-fetal interface. Here, we demonstrate that fetal wastage triggered by prenatal Listeria monocytogenes infection is driven by placental recruitment of CXCL9-producing inflammatory neutrophils and macrophages that promote infiltration of fetal-specific T cells into the decidua. Maternal CD8+ T cells with fetal specificity upregulated expression of the chemokine receptor CXCR3 and, together with neutrophils and macrophages, were essential for L. monocytogenes-induced fetal resorption. Conversely, decidual accumulation of maternal T cells with fetal specificity and fetal wastage were extinguished by CXCR3 blockade or in CXCR3-deficient mice. Remarkably, protection against fetal wastage and in utero L. monocytogenes invasion was maintained even when CXCR3 neutralization was initiated after infection, and this protective effect extended to fetal resorption triggered by partial ablation of immune-suppressive maternal Tregs, which expand during pregnancy to sustain fetal tolerance. Together, our results indicate that functionally overriding chemokine silencing at the maternal-fetal interface promotes the pathogenesis of prenatal infection and suggest that therapeutically reinforcing this pathway represents a universal approach for mitigating immune-mediated pregnancy complications.

Topics: Adoptive Transfer; Ampicillin; Animals; Anti-Bacterial Agents; CD8-Positive T-Lymphocytes; Chemokine CXCL9; Chemokines; Crosses, Genetic; Decidua; Female; Fetal Death; Fetal Resorption; Listeriosis; Macrophages; Male; Maternal-Fetal Exchange; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Neutrophils; Ovalbumin; Peptide Fragments; Pregnancy; Pregnancy Complications, Infectious; Receptors, CXCR3; Spleen; T-Cell Antigen Receptor Specificity; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Up-Regulation; Virulence

A selective inbreeding of approximately 24 generations of albino guinea pigs by brother x sister mating has resulted in two strains, registered IMM/S and IMM/R, with high and low responsiveness, respectively, to ovalbumin-induced respiratory anaphylaxis. The two guinea pig strains differed in their ability to be immunized by the inhalation of antigen and produce antibodies, as well as to develop respiratory anaphylaxis. A correlation between the strength of the anaphylactic reactions and the amount of hemagglutinating antibodies produced was observed. When immunization was carried out by an intradermal injection of ovalbumin (OA), even in small doses incorporated in FCA, guinea pigs from both strains produced hemagglutinating antibodies in nearly the same amount. These antibodies do not influence the ability of the animals to react with a high respectively low anaphylactic response on subsequent challenge by inhalation of OA, neither in the actively sensitized animals nor in passively sensitized animals. However, with repeated inhalations of OA, desensitization occurred in the intradermally immunized high-responders, while the passively immunized high-responders could be provoked several times without any signs of desensitization. No systematical differences between the two strains with regard to sensitivity to inhalations of histamine were demonstrated. The low responders were found to be less resistant to infections than high-responders.

Topics: Aerosols; Anaphylaxis; Animals; Antibodies; Antibody Formation; Female; Fetal Death; Guinea Pigs; Hemagglutination; Immunity, Maternally-Acquired; Immunization; Inbreeding; Litter Size; Ovalbumin; Pregnancy; Respiratory Hypersensitivity