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Waddlia chondrophila induces systemic infection, organ pathology, and elicits Th1-associated humoral immunity in a murine model of genital infection

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ABSTRACT

Waddlia chondrophila is a known bovine abortigenic Chlamydia-related bacterium that has been associated with adverse pregnancy outcomes in human. However, there is a lack of knowledge regarding how W. chondrophila infection spreads, its ability to elicit an immune response and induce pathology. A murine model of genital infection was developed to investigate the pathogenicity and immune response associated with a W. chondrophila infection. Genital inoculation of the bacterial agent resulted in a dose-dependent infection that spread to lumbar lymph nodes and successively to spleen and liver. Bacterial-induced pathology peaked on day 14, characterized by leukocyte infiltration (uterine horn, liver, and spleen), necrosis (liver) and extramedullary hematopoiesis (spleen). Immunohistochemistry demonstrated the presence of a large number of W. chondrophila in the spleen on day 14. Robust IgG titers were detected by day 14 and remained high until day 52. IgG isotypes consisted of high IgG2a, moderate IgG3 and no detectable IgG1, indicating a Th1-associated immune response. This study provides the first evidence that W. chondrophila genital infection is capable of inducing a systemic infection that spreads to major organs, induces uterus, spleen, and liver pathology and elicits a Th1-skewed humoral response. This new animal model will help our understanding of the mechanisms related to intracellular bacteria-induced miscarriages, the most frequent complication of pregnancy that affects one in four women.

No MeSH data available.


Quantification of W. chondrophila in genital and non-genital organs. Mice were infected with live 109W. chondrophila or mock (M). (A) Bacterial burden in uterine horns and cervix/vagina at days 7, 14, and 21 p.i. (B) Bacterial burden in liver, spleen, lumbar lymph nodes, muscle, and blood at days 7, 14, and 21 p.i. qPCR values represent the mean SEM. Results are representative of two independent experiments with n = 3 and 5 for each experiment.
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Figure 2: Quantification of W. chondrophila in genital and non-genital organs. Mice were infected with live 109W. chondrophila or mock (M). (A) Bacterial burden in uterine horns and cervix/vagina at days 7, 14, and 21 p.i. (B) Bacterial burden in liver, spleen, lumbar lymph nodes, muscle, and blood at days 7, 14, and 21 p.i. qPCR values represent the mean SEM. Results are representative of two independent experiments with n = 3 and 5 for each experiment.

Mentions: qPCR analysis on uterine horns and cervix/vagina samples demonstrated a high bacterial burden on days 7, 14, and 21 p.i. (Figure 2A). Infection also spread to lumbar lymph nodes, spleen, and liver (Figure 2B), but bacteria were never identified in blood (data not shown). To assess whether the bacteria in those organs were able to replicate, spleen, and liver homogenates were incubated with McCoy cells for 7 days, but no replication was observed (data not shown). Vaginal shedding was resolved 7 days post-infection (< 101 copies/μl), and replicating bacteria were still present at days 2 and 4 post-infection (data not shown).


Waddlia chondrophila induces systemic infection, organ pathology, and elicits Th1-associated humoral immunity in a murine model of genital infection
Quantification of W. chondrophila in genital and non-genital organs. Mice were infected with live 109W. chondrophila or mock (M). (A) Bacterial burden in uterine horns and cervix/vagina at days 7, 14, and 21 p.i. (B) Bacterial burden in liver, spleen, lumbar lymph nodes, muscle, and blood at days 7, 14, and 21 p.i. qPCR values represent the mean SEM. Results are representative of two independent experiments with n = 3 and 5 for each experiment.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631992&req=5

Figure 2: Quantification of W. chondrophila in genital and non-genital organs. Mice were infected with live 109W. chondrophila or mock (M). (A) Bacterial burden in uterine horns and cervix/vagina at days 7, 14, and 21 p.i. (B) Bacterial burden in liver, spleen, lumbar lymph nodes, muscle, and blood at days 7, 14, and 21 p.i. qPCR values represent the mean SEM. Results are representative of two independent experiments with n = 3 and 5 for each experiment.
Mentions: qPCR analysis on uterine horns and cervix/vagina samples demonstrated a high bacterial burden on days 7, 14, and 21 p.i. (Figure 2A). Infection also spread to lumbar lymph nodes, spleen, and liver (Figure 2B), but bacteria were never identified in blood (data not shown). To assess whether the bacteria in those organs were able to replicate, spleen, and liver homogenates were incubated with McCoy cells for 7 days, but no replication was observed (data not shown). Vaginal shedding was resolved 7 days post-infection (< 101 copies/μl), and replicating bacteria were still present at days 2 and 4 post-infection (data not shown).

View Article: PubMed Central

ABSTRACT

Waddlia chondrophila is a known bovine abortigenic Chlamydia-related bacterium that has been associated with adverse pregnancy outcomes in human. However, there is a lack of knowledge regarding how W. chondrophila infection spreads, its ability to elicit an immune response and induce pathology. A murine model of genital infection was developed to investigate the pathogenicity and immune response associated with a W. chondrophila infection. Genital inoculation of the bacterial agent resulted in a dose-dependent infection that spread to lumbar lymph nodes and successively to spleen and liver. Bacterial-induced pathology peaked on day 14, characterized by leukocyte infiltration (uterine horn, liver, and spleen), necrosis (liver) and extramedullary hematopoiesis (spleen). Immunohistochemistry demonstrated the presence of a large number of W. chondrophila in the spleen on day 14. Robust IgG titers were detected by day 14 and remained high until day 52. IgG isotypes consisted of high IgG2a, moderate IgG3 and no detectable IgG1, indicating a Th1-associated immune response. This study provides the first evidence that W. chondrophila genital infection is capable of inducing a systemic infection that spreads to major organs, induces uterus, spleen, and liver pathology and elicits a Th1-skewed humoral response. This new animal model will help our understanding of the mechanisms related to intracellular bacteria-induced miscarriages, the most frequent complication of pregnancy that affects one in four women.

No MeSH data available.