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Intrauterine Candida albicans infection elicits severe inflammation in fetal sheep.

Payne MS, Kemp MW, Kallapur SG, Kannan PS, Saito M, Miura Y, Newnham JP, Stock S, Ireland DJ, Kramer BW, Jobe AH - Pediatr. Res. (2014)

Bottom Line: Colonization of the amniotic cavity by C. albicans resulted in a modest inflammatory response at 1 d and florid inflammation at 2 d, characterized by fetal thrombocytopenia, lymphopenia, and significant increases of inflammatory cytokines/chemokines in the fetal membranes skin, lung, and the amniotic fluid.Acute colonization of the amniotic cavity by C. albicans causes severe intrauterine inflammation and fetal injury.C. albicans is a potent fetal pathogen that can contribute to adverse pregnancy outcomes.

View Article: PubMed Central - PubMed

Affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.

ABSTRACT

Background: Preventing preterm birth and subsequent adverse neonatal sequelae is among the greatest clinical challenges of our time. Recent studies suggest a role for Candida spp. in preterm birth and fetal injury, as a result of their colonization of either the vagina and/or the amniotic cavity. We hypothesized that intraamniotic Candida albicans would cause a vigorous, acute fetal inflammatory response.

Methods: Sheep carrying singleton pregnancies received single intraamniotic injections of either saline (control) or 10(7) colony-forming units C. albicans 1 or 2 d prior to surgical delivery and euthanasia at 124 ± 2 d gestation.

Results: Colonization of the amniotic cavity by C. albicans resulted in a modest inflammatory response at 1 d and florid inflammation at 2 d, characterized by fetal thrombocytopenia, lymphopenia, and significant increases of inflammatory cytokines/chemokines in the fetal membranes skin, lung, and the amniotic fluid.

Conclusion: Acute colonization of the amniotic cavity by C. albicans causes severe intrauterine inflammation and fetal injury. C. albicans is a potent fetal pathogen that can contribute to adverse pregnancy outcomes.

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Panel A: Expression of cytokine/chemokine mRNA is increased in the fetal lung in response to 2 d C. albicans exposure. Black bars, Control n=13; Grey bars, 1 d Candida n=8; Hatched bars, 2 d Candida n=8. * p<0.05 vs. control; † p<0.05 vs. 1 d C. albicans exposure. Panel B: Expression of cytokine/chemokine mRNA is variably increased in the fetal skin in response to 1 d and 2 d C. albicans exposure. Black bars, control n=6; Grey bars, 1 d Candida n=5; Hatched bars, 2 d Candida n=6. * p<0.05 vs. control; † p<0.05 vs. 1 d C. albicans exposure. Panel C: Only IL-8 is significantly increased in the chorioamnion in response to 1 d and 2 d C. albicans exposure. Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=5) * p<0.05 vs. control.
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Figure 3: Panel A: Expression of cytokine/chemokine mRNA is increased in the fetal lung in response to 2 d C. albicans exposure. Black bars, Control n=13; Grey bars, 1 d Candida n=8; Hatched bars, 2 d Candida n=8. * p<0.05 vs. control; † p<0.05 vs. 1 d C. albicans exposure. Panel B: Expression of cytokine/chemokine mRNA is variably increased in the fetal skin in response to 1 d and 2 d C. albicans exposure. Black bars, control n=6; Grey bars, 1 d Candida n=5; Hatched bars, 2 d Candida n=6. * p<0.05 vs. control; † p<0.05 vs. 1 d C. albicans exposure. Panel C: Only IL-8 is significantly increased in the chorioamnion in response to 1 d and 2 d C. albicans exposure. Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=5) * p<0.05 vs. control.

Mentions: Analysis of cytokine/chemokine expression in the fetal lung, skin and membranes identified a pattern of significant mRNA up-regulation at 2 d post-C. albicans infection, relative to both control and 1 d post-C. albicans infection tissues. Significant increases in IL-1β (p=0.007), IL-6 (p=0.007), IL-8 (p=0.010), TNF-α (p=0.003) and MCP-1 (p=0.003) mRNA expression were identified in the fetal lung at 2 d post-infection, relative to control (Figure 3a). In the fetal skin, significant mRNA increases were observed in the expression of IL-6 at 2 d (p=0.004), TNF-α at 2 d (p=0.019), IL-8 at 1 d (p=0.000) and 2 d (p=0.000), and MCP-2 at 1 d (p=0.031) and 2 d (p=0.000) post-C. albicans infection, relative to control (Figure 3b). In fetal membranes, a significant increase was only observed in IL-8 mRNA expression (p=0.020) at 2 d post-C. albicans infection, relative to control (Figure 3c).


Intrauterine Candida albicans infection elicits severe inflammation in fetal sheep.

Payne MS, Kemp MW, Kallapur SG, Kannan PS, Saito M, Miura Y, Newnham JP, Stock S, Ireland DJ, Kramer BW, Jobe AH - Pediatr. Res. (2014)

Panel A: Expression of cytokine/chemokine mRNA is increased in the fetal lung in response to 2 d C. albicans exposure. Black bars, Control n=13; Grey bars, 1 d Candida n=8; Hatched bars, 2 d Candida n=8. * p<0.05 vs. control; † p<0.05 vs. 1 d C. albicans exposure. Panel B: Expression of cytokine/chemokine mRNA is variably increased in the fetal skin in response to 1 d and 2 d C. albicans exposure. Black bars, control n=6; Grey bars, 1 d Candida n=5; Hatched bars, 2 d Candida n=6. * p<0.05 vs. control; † p<0.05 vs. 1 d C. albicans exposure. Panel C: Only IL-8 is significantly increased in the chorioamnion in response to 1 d and 2 d C. albicans exposure. Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=5) * p<0.05 vs. control.
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Figure 3: Panel A: Expression of cytokine/chemokine mRNA is increased in the fetal lung in response to 2 d C. albicans exposure. Black bars, Control n=13; Grey bars, 1 d Candida n=8; Hatched bars, 2 d Candida n=8. * p<0.05 vs. control; † p<0.05 vs. 1 d C. albicans exposure. Panel B: Expression of cytokine/chemokine mRNA is variably increased in the fetal skin in response to 1 d and 2 d C. albicans exposure. Black bars, control n=6; Grey bars, 1 d Candida n=5; Hatched bars, 2 d Candida n=6. * p<0.05 vs. control; † p<0.05 vs. 1 d C. albicans exposure. Panel C: Only IL-8 is significantly increased in the chorioamnion in response to 1 d and 2 d C. albicans exposure. Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=5) * p<0.05 vs. control.
Mentions: Analysis of cytokine/chemokine expression in the fetal lung, skin and membranes identified a pattern of significant mRNA up-regulation at 2 d post-C. albicans infection, relative to both control and 1 d post-C. albicans infection tissues. Significant increases in IL-1β (p=0.007), IL-6 (p=0.007), IL-8 (p=0.010), TNF-α (p=0.003) and MCP-1 (p=0.003) mRNA expression were identified in the fetal lung at 2 d post-infection, relative to control (Figure 3a). In the fetal skin, significant mRNA increases were observed in the expression of IL-6 at 2 d (p=0.004), TNF-α at 2 d (p=0.019), IL-8 at 1 d (p=0.000) and 2 d (p=0.000), and MCP-2 at 1 d (p=0.031) and 2 d (p=0.000) post-C. albicans infection, relative to control (Figure 3b). In fetal membranes, a significant increase was only observed in IL-8 mRNA expression (p=0.020) at 2 d post-C. albicans infection, relative to control (Figure 3c).

Bottom Line: Colonization of the amniotic cavity by C. albicans resulted in a modest inflammatory response at 1 d and florid inflammation at 2 d, characterized by fetal thrombocytopenia, lymphopenia, and significant increases of inflammatory cytokines/chemokines in the fetal membranes skin, lung, and the amniotic fluid.Acute colonization of the amniotic cavity by C. albicans causes severe intrauterine inflammation and fetal injury.C. albicans is a potent fetal pathogen that can contribute to adverse pregnancy outcomes.

View Article: PubMed Central - PubMed

Affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.

ABSTRACT

Background: Preventing preterm birth and subsequent adverse neonatal sequelae is among the greatest clinical challenges of our time. Recent studies suggest a role for Candida spp. in preterm birth and fetal injury, as a result of their colonization of either the vagina and/or the amniotic cavity. We hypothesized that intraamniotic Candida albicans would cause a vigorous, acute fetal inflammatory response.

Methods: Sheep carrying singleton pregnancies received single intraamniotic injections of either saline (control) or 10(7) colony-forming units C. albicans 1 or 2 d prior to surgical delivery and euthanasia at 124 ± 2 d gestation.

Results: Colonization of the amniotic cavity by C. albicans resulted in a modest inflammatory response at 1 d and florid inflammation at 2 d, characterized by fetal thrombocytopenia, lymphopenia, and significant increases of inflammatory cytokines/chemokines in the fetal membranes skin, lung, and the amniotic fluid.

Conclusion: Acute colonization of the amniotic cavity by C. albicans causes severe intrauterine inflammation and fetal injury. C. albicans is a potent fetal pathogen that can contribute to adverse pregnancy outcomes.

Show MeSH
Related in: MedlinePlus