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

Serological responses in ewes that aborted (includes non-viable births and stillbirths) (-▴-) and lambed (-▪-) following intranasal inoculation with 5×103 (A; Group 1), 5×105 (B; Group 2) or 5×107 (C; Group 3) IFU C. abortus or intranasally administered negative control inoculum (D; Group 4a; all lambed) (…x…) prior to pregnancy, or subcutaneously injected with 2×106 IFU at 70 days of gestation (D; Group 5).Means (± SEM) of normalised responses (see Materials and Methods) are shown. 100% is equivalent to an OD450nm of 2.25. The lambing/abortion periods for years 1 and 2 are indicated by the horizontal double-headed arrows. Year 1 only for Groups 4a and 5 (D).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585262&req=5

pone-0057950-g003: Serological responses in ewes that aborted (includes non-viable births and stillbirths) (-▴-) and lambed (-▪-) following intranasal inoculation with 5×103 (A; Group 1), 5×105 (B; Group 2) or 5×107 (C; Group 3) IFU C. abortus or intranasally administered negative control inoculum (D; Group 4a; all lambed) (…x…) prior to pregnancy, or subcutaneously injected with 2×106 IFU at 70 days of gestation (D; Group 5).Means (± SEM) of normalised responses (see Materials and Methods) are shown. 100% is equivalent to an OD450nm of 2.25. The lambing/abortion periods for years 1 and 2 are indicated by the horizontal double-headed arrows. Year 1 only for Groups 4a and 5 (D).

Mentions: Ewes were blood sampled prior to inoculation and at regular intervals throughout the course of the two lambing seasons. Following intranasal challenge, the highest and most rapid mean antibody responses were observed in group 3 animals, which received the highest dose of Chlamydia (Figure 3). All except 2 of the group 3 ewes (19 pregnant ewes; Table 1) were positive (>60%) at two weeks after inoculation. The mean antibody responses were lower and occurred slightly later in group 2 animals, where the challenge dose was less: 13 out of 18 ewes were positive 2 weeks after challenge. In group 1, where the lowest dose of Chlamydia was administered, only one of 16 animals had seroconverted two weeks after infection, which had only increased to 9 ewes by 5 weeks post infection.


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)

Serological responses in ewes that aborted (includes non-viable births and stillbirths) (-▴-) and lambed (-▪-) following intranasal inoculation with 5×103 (A; Group 1), 5×105 (B; Group 2) or 5×107 (C; Group 3) IFU C. abortus or intranasally administered negative control inoculum (D; Group 4a; all lambed) (…x…) prior to pregnancy, or subcutaneously injected with 2×106 IFU at 70 days of gestation (D; Group 5).Means (± SEM) of normalised responses (see Materials and Methods) are shown. 100% is equivalent to an OD450nm of 2.25. The lambing/abortion periods for years 1 and 2 are indicated by the horizontal double-headed arrows. Year 1 only for Groups 4a and 5 (D).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0057950-g003: Serological responses in ewes that aborted (includes non-viable births and stillbirths) (-▴-) and lambed (-▪-) following intranasal inoculation with 5×103 (A; Group 1), 5×105 (B; Group 2) or 5×107 (C; Group 3) IFU C. abortus or intranasally administered negative control inoculum (D; Group 4a; all lambed) (…x…) prior to pregnancy, or subcutaneously injected with 2×106 IFU at 70 days of gestation (D; Group 5).Means (± SEM) of normalised responses (see Materials and Methods) are shown. 100% is equivalent to an OD450nm of 2.25. The lambing/abortion periods for years 1 and 2 are indicated by the horizontal double-headed arrows. Year 1 only for Groups 4a and 5 (D).
Mentions: Ewes were blood sampled prior to inoculation and at regular intervals throughout the course of the two lambing seasons. Following intranasal challenge, the highest and most rapid mean antibody responses were observed in group 3 animals, which received the highest dose of Chlamydia (Figure 3). All except 2 of the group 3 ewes (19 pregnant ewes; Table 1) were positive (>60%) at two weeks after inoculation. The mean antibody responses were lower and occurred slightly later in group 2 animals, where the challenge dose was less: 13 out of 18 ewes were positive 2 weeks after challenge. In group 1, where the lowest dose of Chlamydia was administered, only one of 16 animals had seroconverted two weeks after infection, which had only increased to 9 ewes by 5 weeks post infection.

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