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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:C. albicans RNA in fetal tissues in 1 d and 2 d post-infection groups. (1 d Candida n=5; 2 d Candida n=5). CHR, chorioamnion; SK, skin; RLL, right lower lobe of lung. *, significant difference (p < 0.010) vs. RUL. Panel B: Concentration of IL-1β (Black bars, Control n=10; Grey bars, 1 d Candida n=8; Hatched bars, 2 d Candida n=8) and IL-8 (Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=6), but not IL-6 (Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=6;) is increased in AF in response to IAI with C. albicans. * p<0.05 vs. control; † p<0.05 vs. 1 d Candida albicans exposure.
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Figure 1: Panel A:C. albicans RNA in fetal tissues in 1 d and 2 d post-infection groups. (1 d Candida n=5; 2 d Candida n=5). CHR, chorioamnion; SK, skin; RLL, right lower lobe of lung. *, significant difference (p < 0.010) vs. RUL. Panel B: Concentration of IL-1β (Black bars, Control n=10; Grey bars, 1 d Candida n=8; Hatched bars, 2 d Candida n=8) and IL-8 (Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=6), but not IL-6 (Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=6;) is increased in AF in response to IAI with C. albicans. * p<0.05 vs. control; † p<0.05 vs. 1 d Candida albicans exposure.

Mentions: Amniotic fluid from all 1 d and 2 d C. albicans exposed animals but none of the controls were positive for viable C. albicans growth (data not shown). qPCR analysis demonstrated increased C. albicans RNA in fetal lung (3.8 ± 3 ng), chorioamnion (78 ± 32 ng) and skin (50 ± 48 ng) taken from animals exposed to C. albicans for 2 d, relative to fetal lung (0.2 ng ± 0.1 ng), chorioamnion (14 ± 10 ng) and skin (6.0 ± 5.0 ng) exposed to C. albicans for 1 d (Figure 1a). The highest levels of C. albicans RNA were detected in chorioamnion tissue after a 2 d exposure (p < 0.010 vs. 2 d fetal lung). No C. albicans RNA was detected in the fetal spleen after either 1 d or 2 d C. albicans exposure or in any saline control animal.


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:C. albicans RNA in fetal tissues in 1 d and 2 d post-infection groups. (1 d Candida n=5; 2 d Candida n=5). CHR, chorioamnion; SK, skin; RLL, right lower lobe of lung. *, significant difference (p < 0.010) vs. RUL. Panel B: Concentration of IL-1β (Black bars, Control n=10; Grey bars, 1 d Candida n=8; Hatched bars, 2 d Candida n=8) and IL-8 (Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=6), but not IL-6 (Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=6;) is increased in AF in response to IAI with C. albicans. * p<0.05 vs. control; † p<0.05 vs. 1 d Candida albicans exposure.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4530618&req=5

Figure 1: Panel A:C. albicans RNA in fetal tissues in 1 d and 2 d post-infection groups. (1 d Candida n=5; 2 d Candida n=5). CHR, chorioamnion; SK, skin; RLL, right lower lobe of lung. *, significant difference (p < 0.010) vs. RUL. Panel B: Concentration of IL-1β (Black bars, Control n=10; Grey bars, 1 d Candida n=8; Hatched bars, 2 d Candida n=8) and IL-8 (Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=6), but not IL-6 (Black bars, Control n=6; Grey bars, 1 d Candida n=6; Hatched bars, 2 d Candida n=6;) is increased in AF in response to IAI with C. albicans. * p<0.05 vs. control; † p<0.05 vs. 1 d Candida albicans exposure.
Mentions: Amniotic fluid from all 1 d and 2 d C. albicans exposed animals but none of the controls were positive for viable C. albicans growth (data not shown). qPCR analysis demonstrated increased C. albicans RNA in fetal lung (3.8 ± 3 ng), chorioamnion (78 ± 32 ng) and skin (50 ± 48 ng) taken from animals exposed to C. albicans for 2 d, relative to fetal lung (0.2 ng ± 0.1 ng), chorioamnion (14 ± 10 ng) and skin (6.0 ± 5.0 ng) exposed to C. albicans for 1 d (Figure 1a). The highest levels of C. albicans RNA were detected in chorioamnion tissue after a 2 d exposure (p < 0.010 vs. 2 d fetal lung). No C. albicans RNA was detected in the fetal spleen after either 1 d or 2 d C. albicans exposure or in any saline control animal.

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