Dataset Information

Cytokine dysregulation in early- and late-term placentas from feline immunodeficiency virus (FIV)-infected cats.

ABSTRACT: Experimental infection of cats with FIV-B-2542 produces high rates of fetal infection and reproductive failure. We hypothesized that dysregulation of placental cytokine expression occurs in FIV-infected queens, and aberrant expression potentiates inflammation and impacts pregnancy outcome. Our purpose was to quantify expression of representative pro-inflammatory cytokines (IL-6, IL-12p35, and IL-1?), IL-10 (anti-inflammatory), and the chemokine SDF-1? in early- and late-term placental tissues.?Real-time reverse transcriptase PCR was used to measure gene expression in placental tissues.?Increased expression of IL-6 and IL-12p35 and decreased expression of IL-10 occurred in FIV-infected tissues at early pregnancy; at late gestation, IL-6 expression increased and IL-1? and SDF-1? decreased. At late pregnancy, IL-6 expression positively correlated with FIV load. IL-12:IL-10 ratios were higher in infected tissues at early, but not late pregnancy. Fetal non-viability accompanied decreased IL-12p35 and SDF-1? expression at both stages and decreased IL-12:IL-10 ratio at late pregnancy.FIV infection caused a pro-inflammatory placental microenvironment at early, but not late pregnancy.

SUBMITTER: Scott VL

PROVIDER: S-EPMC3005979 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Cytokine dysregulation in early- and late-term placentas from feline immunodeficiency virus (FIV)-infected cats.

Scott Veronica L VL Boudreaux Crystal E CE Lockett Nikki N NN Clay Brittany T BT Coats Karen S KS

American journal of reproductive immunology (New York, N.Y. : 1989) 20100906 5

<h4>Problem</h4>Experimental infection of cats with FIV-B-2542 produces high rates of fetal infection and reproductive failure. We hypothesized that dysregulation of placental cytokine expression occurs in FIV-infected queens, and aberrant expression potentiates inflammation and impacts pregnancy outcome. Our purpose was to quantify expression of representative pro-inflammatory cytokines (IL-6, IL-12p35, and IL-1β), IL-10 (anti-inflammatory), and the chemokine SDF-1α in early- and late-term plac ...[more]

PMID: 20825375

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Project description:FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection may cause dysregulation of trophoblast immunomodulator expression, and aberrant expression of these molecules may potentiate inflammation and compromise pregnancy. The purpose of this project was to evaluate the expression of representative pro-(TNF-?, IFN-?, IL-1?, IL-2, IL-6, IL-12p35, IL-12p40, IL-18, and GM-CSF) and anti-inflammatory cytokines (IL-4, IL-5, and IL-10); CD134, a secondary co-stimulatory molecule expressed on activated T cells (FIV primary receptor); the chemokine receptor CXCR4 (FIV co-receptor); SDF-1?, the chemokine ligand to CXCR4; and FIV gag in trophoblasts from early-and late-term pregnancy.We used an anti-cytokeratin antibody in immunohistochemistry to identify trophoblasts selectively, collected these cells using laser capture microdissection, and extracted total RNA from the captured cell populations. Real time, reverse transcription-PCR was used to quantify gene expression.We detected IL-4, IL-5, IL-6, IL-1?, IL-12p35, IL-12p40, and CXCR4 in trophoblasts from early-and late-term pregnancy. Expression of cytokines increased from early to late pregnancy in normal tissues. A clear, pro-inflammatory microenvironment was not evident in trophoblasts from FIV-infected queens at either stage of pregnancy. Reproductive failure was accompanied by down-regulation of both pro-and anti-inflammatory cytokines. CD134 was not detected in trophoblasts, and FIV gag was detected in only one of ten trophoblast specimens collected from FIV-infected queens.Feline trophoblasts express an array of pro-and anti-inflammatory immunomodulators whose expression increases from early to late pregnancy in normal tissues. Non-viable pregnancies were associated with decreased expression of immunomodulators which regulate trophoblast invasion in other species. The detection of FIV RNA in trophoblasts was rare, suggesting that the high rate of reproductive failure in FIV-infected queens was not a direct result of viral replication in trophoblasts. The influence of placental immune cells on trophoblast function and pregnancy maintenance in the FIV-infected cat requires additional study.

Project description:Although the antibody response induced by primary vaccination with Fel-O-Vax® FIV (three doses, 2-4 weeks apart) is well described, the antibody response induced by annual vaccination with Fel-O-Vax® FIV (single dose every 12 months after primary vaccination) and how it compares to the primary antibody response has not been studied. Residual blood samples from a primary FIV vaccination study (n = 11), and blood samples from cats given an annual FIV vaccination (n = 10), were utilized. Samples from all 21 cats were tested with a commercially available PCR assay (FIV RealPCRTM), an anti-p24 microsphere immunoassay (MIA), an anti-FIV transmembrane (TM; gp40) peptide ELISA, and a range of commercially available point-of-care (PoC) FIV antibody kits. PCR testing confirmed all 21 cats to be FIV-uninfected for the duration of this study. Results from MIA and ELISA testing showed that both vaccination regimes induced significant antibody responses against p24 and gp40, and both anti-p24 and anti-gp40 antibodies were variably present 12 months after FIV vaccination. The magnitude of the antibody response against both p24 and gp40 was significantly higher in the primary FIV vaccination group than in the annual FIV vaccination group. The differences in prime versus recall post-vaccinal antibody levels correlated with FIV PoC kit performance. Two FIV PoC kits that detect antibodies against gp40, namely Witness® and Anigen Rapid®, showed 100% specificity in cats recently administered an annual FIV vaccination, demonstrating that they can be used to accurately distinguish vaccination and infection in annually vaccinated cats. A third FIV PoC kit, SNAP® Combo, had 0% specificity in annually FIV-vaccinated cats, and should not be used in any cat with a possible history of FIV vaccination. This study outlines the antibody response to inactivated Fel-O-Vax® FIV whole-virus vaccine, and demonstrates how best to diagnose FIV infection in jurisdictions where FIV vaccination is practiced.

Dataset Information

Cytokine dysregulation in early- and late-term placentas from feline immunodeficiency virus (FIV)-infected cats.

Publications

Cytokine dysregulation in early- and late-term placentas from feline immunodeficiency virus (FIV)-infected cats.

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