Limits...
Intranasal infection with Chlamydia abortus induces dose-dependent latency and abortion in sheep.

Longbottom D, Livingstone M, Maley S, van der Zon A, Rocchi M, Wilson K, Wheelhouse N, Dagleish M, Aitchison K, Wattegedera S, Nath M, Entrican G, Buxton D - PLoS ONE (2013)

Bottom Line: Three groups of sheep (groups 1, 2 and 3) were experimentally infected with different doses of C. abortus (5×10(3), 5×10(5) and 5×10(7) inclusion forming units (IFU), respectively) prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes.Two further groups received either negative control inoculum (group 4a,b) or were inoculated subcutaneously on day 70 of gestation with 2×10(6) IFU C. abortus (group 5).Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium.

View Article: PubMed Central - PubMed

Affiliation: Moredun Research Institute, Edinburgh, United Kingdom. david.longbottom@moredun.ac.uk

ABSTRACT

Background: Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus.

Methodology/principal findings: Three groups of sheep (groups 1, 2 and 3) were experimentally infected with different doses of C. abortus (5×10(3), 5×10(5) and 5×10(7) inclusion forming units (IFU), respectively) prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b) or were inoculated subcutaneously on day 70 of gestation with 2×10(6) IFU C. abortus (group 5). Animals in groups 1, 2 and 5 experienced an abortion rate of 50-67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium.

Conclusions/significance: The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and vaccines for controlling infection.

Show MeSH

Related in: MedlinePlus

Number of ewes recorded daily with elevated (≥40°C) rectal temperatures following intranasal inoculation with 5×103 (Group 1), 5×105 (Group 2) or 5×107 (Group 3) IFU C. abortus, or subcutaneously injected with 2×106 IFU at 70 days of gestation (Group 5). None of the ewes inoculated with control inoculum (Group 4a) developed elevated rectal temperatures.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585262&req=5

pone-0057950-g001: Number of ewes recorded daily with elevated (≥40°C) rectal temperatures following intranasal inoculation with 5×103 (Group 1), 5×105 (Group 2) or 5×107 (Group 3) IFU C. abortus, or subcutaneously injected with 2×106 IFU at 70 days of gestation (Group 5). None of the ewes inoculated with control inoculum (Group 4a) developed elevated rectal temperatures.

Mentions: Groups 1–4 were inoculated prior to mating and group 5 at 70 days of gestation (dg) and the rectal temperature readings recorded (Figure 1). Only ewes that developed an elevated temperature (≥40°C) from day 2 post inoculation (dpi) onwards were considered for further analysis, as temperature events prior to this time were considered to have been influenced by handling and so were disregarded. A total of 16 of the starting 21 non-pregnant ewes from group 3 were recorded as having developed a fever, which occurred from day 2 post inoculation (dpi) until day 10. The group 2 animals developed a raised temperature from 10–14 dpi that affected 6 of the non-pregnant ewes and 6 of the ewes in group 3 had short-lived febrile episodes from 14–23 dpi. No febrile responses were recorded for the 8 non-pregnant ewes in group 4a. In group 5, 5 of the 6 pregnant ewes were recorded as febrile from 3 to 5 dpi.


Intranasal infection with Chlamydia abortus induces dose-dependent latency and abortion in sheep.

Longbottom D, Livingstone M, Maley S, van der Zon A, Rocchi M, Wilson K, Wheelhouse N, Dagleish M, Aitchison K, Wattegedera S, Nath M, Entrican G, Buxton D - PLoS ONE (2013)

Number of ewes recorded daily with elevated (≥40°C) rectal temperatures following intranasal inoculation with 5×103 (Group 1), 5×105 (Group 2) or 5×107 (Group 3) IFU C. abortus, or subcutaneously injected with 2×106 IFU at 70 days of gestation (Group 5). None of the ewes inoculated with control inoculum (Group 4a) developed elevated rectal temperatures.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585262&req=5

pone-0057950-g001: Number of ewes recorded daily with elevated (≥40°C) rectal temperatures following intranasal inoculation with 5×103 (Group 1), 5×105 (Group 2) or 5×107 (Group 3) IFU C. abortus, or subcutaneously injected with 2×106 IFU at 70 days of gestation (Group 5). None of the ewes inoculated with control inoculum (Group 4a) developed elevated rectal temperatures.
Mentions: Groups 1–4 were inoculated prior to mating and group 5 at 70 days of gestation (dg) and the rectal temperature readings recorded (Figure 1). Only ewes that developed an elevated temperature (≥40°C) from day 2 post inoculation (dpi) onwards were considered for further analysis, as temperature events prior to this time were considered to have been influenced by handling and so were disregarded. A total of 16 of the starting 21 non-pregnant ewes from group 3 were recorded as having developed a fever, which occurred from day 2 post inoculation (dpi) until day 10. The group 2 animals developed a raised temperature from 10–14 dpi that affected 6 of the non-pregnant ewes and 6 of the ewes in group 3 had short-lived febrile episodes from 14–23 dpi. No febrile responses were recorded for the 8 non-pregnant ewes in group 4a. In group 5, 5 of the 6 pregnant ewes were recorded as febrile from 3 to 5 dpi.

Bottom Line: Three groups of sheep (groups 1, 2 and 3) were experimentally infected with different doses of C. abortus (5×10(3), 5×10(5) and 5×10(7) inclusion forming units (IFU), respectively) prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes.Two further groups received either negative control inoculum (group 4a,b) or were inoculated subcutaneously on day 70 of gestation with 2×10(6) IFU C. abortus (group 5).Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium.

View Article: PubMed Central - PubMed

Affiliation: Moredun Research Institute, Edinburgh, United Kingdom. david.longbottom@moredun.ac.uk

ABSTRACT

Background: Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus.

Methodology/principal findings: Three groups of sheep (groups 1, 2 and 3) were experimentally infected with different doses of C. abortus (5×10(3), 5×10(5) and 5×10(7) inclusion forming units (IFU), respectively) prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b) or were inoculated subcutaneously on day 70 of gestation with 2×10(6) IFU C. abortus (group 5). Animals in groups 1, 2 and 5 experienced an abortion rate of 50-67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium.

Conclusions/significance: The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and vaccines for controlling infection.

Show MeSH
Related in: MedlinePlus