Defining immune correlates during latent and active chlamydial infection in sheep

Sean R Wattegedera,Kevin Aitchison,Stephen Maley,Mara Rocchi,Morag Livingstone,Javier Palarea-Albaladejo,David Longbottom,Susan Lee,David Buxton,Yvonne Pang,Nick M Wheelhouse,Gary Entrican

doi:10.1186/s13567-020-00798-6

Abstract

Ovine enzootic abortion (OEA) caused by the obligate intracellular bacterial pathogen Chlamydia abortus (C. abortus), is an endemic disease in most sheep-rearing countries worldwide. Following infection, C. abortus establishes a complex host–pathogen interaction with a latent phase in non-pregnant sheep followed by an active disease phase in the placenta during pregnancy leading to OEA. Improved knowledge of the host–pathogen interactions at these different phases of disease will accelerate the development of new diagnostic tests and vaccines to control OEA. Current evidence indicates that cellular immunity is essential for controlling C. abortus infection. We have previously described a model of mucosal (intranasal) infection of non-pregnant sheep with C. abortus that replicates the latent and active phases of OEA. We have investigated antigen-specific recall responses of peripheral blood mononuclear cells (PBMC) in sheep infected with C. abortus via the intranasal route to determine how these change during the latent and active phases of disease. By analysing cytokines associated with the major CD4+ve Thelper (Th) cell subsets (Interferon-gamma (IFN-γ)/Th1; Interleukin (IL)-4/Th2; IL-17A/Th17; IL-10/Tregulatory), we show that there is selective activation of PBMC producing IFN-γ and/or IL-10 during the latent phase following infection. These cytokines are also elevated during the active disease phase and while they are produced by sheep that are protected from OEA, they are also produced by sheep that abort, highlighting the difficulties in finding specific cellular immunological correlates of protection for complex intracellular pathogens.

Highlights

Chlamydia abortus (C. abortus) is a common infectious cause of ovine abortion world-wide despite the availability of commercial vaccines [1, 2]
Responses of each animal are represented by a single bar, with red bars indicating the animals excluded from the study based on a combination of the cut-off criteria listed in Table 1
The retained animals were ranked by the magnitude of their peripheral blood mononuclear cells (PBMC) to produce IFN-γ in response to Concanavalin A (ConA)

Summary

Introduction

Chlamydia abortus (C. abortus) is a common infectious cause of ovine abortion world-wide (with the exception of Australia and New Zealand) despite the availability of commercial vaccines [1, 2]. DIVA (Differentiating Infected from Vaccinated Animals) test is a further complicating factor in the implementation of effective disease control strategies [7]. The development of new control strategies incorporating a DIVA approach is hampered by a relatively poor understanding of how immune responses at different stages of infection relate to disease outcome. Primary infection of non-pregnant sheep can result in an asymptomatic, latent infection that leads to colonisation of placental trophoblast cells in the subsequent pregnancy, destruction of the chorionic epithelium and abortions that manifest in the last 2–3 weeks of gestation [1, Wattegedera et al Vet Res (2020) 51:75

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