Abstract

BackgroundLatency 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 FindingsThree groups of sheep (groups 1, 2 and 3) were experimentally infected with different doses of C. abortus (5×103, 5×105 and 5×107 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 2×106 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/SignificanceThe 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.

Highlights

  • The obligate, intracellular, Gram-negative bacterium Chlamydia abortus (C. abortus) is recognised as a major cause of abortion and lamb loss throughout the world, with infection resulting in the disease known as Enzootic Abortion of Ewes (EAE) or Ovine Enzootic Abortion (OEA) [1]

  • As a working hypothesis it is suggested that following intranasal administration, chlamydial organisms adhere to the pharyngeal mucosa and are taken up by the nasal-associated lymphoid tissue (NALT), and possibly by the tonsils, to initiate infection

  • The outcome of infection was dependent upon the dose given, with lower doses manifesting in higher abortion rates than a high dose

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Summary

Introduction

The obligate, intracellular, Gram-negative bacterium Chlamydia abortus (C. abortus) is recognised as a major cause of abortion and lamb loss throughout the world, with infection resulting in the disease known as Enzootic Abortion of Ewes (EAE) or Ovine Enzootic Abortion (OEA) [1]. Studies on the pathogenesis of infection have shown that lesions are mostly confined to the placental membranes [5,6], they may occur in the brain and liver of foetuses [7]. The fact that typical abortions are seen in the last few weeks of pregnancy [2,3] correlates with the finding that experimentally-induced placental lesions are initiated at the same time and develop progressively from 110 days of gestation (dg) [5,9]. 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. 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 nonpregnant sheep with C. abortus

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