Defining immune correlates during latent and active chlamydial infection in sheep

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

doi:10.1186/s13567-020-00798-6

Defining immune correlates during latent and active chlamydial infection in sheep

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

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	75
Journal	Veterinary Research
Volume	51
Issue number	1
DOIs	https://doi.org/10.1186/s13567-020-00798-6
Publication status	Published - 1 Jun 2020

Access to Document

10.1186/s13567-020-00798-6

S13567 020 00798 6
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Final published version, 3.88 MBLicence: Creative Commons: Attribution (CC-BY)

Cite this

@article{515fe5459c0e40e7b836f6f251bf20c1,

title = "Defining immune correlates during latent and active chlamydial infection in sheep",

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.",

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

year = "2020",

month = jun,

day = "1",

doi = "10.1186/s13567-020-00798-6",

language = "English",

volume = "51",

pages = "75",

journal = "Veterinary Research",

issn = "0928-4249",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Defining immune correlates during latent and active chlamydial infection in sheep

AU - Wattegedera, Sean R

AU - Livingstone, Morag

AU - Maley, Stephen

AU - Rocchi, Mara

AU - Lee, Susan

AU - Pang, Yvonne

AU - Wheelhouse, Nick M

AU - Aitchison, Kevin

AU - Palarea-Albaladejo, Javier

AU - Buxton, David

AU - Longbottom, David

AU - Entrican, Gary

PY - 2020/6/1

Y1 - 2020/6/1

N2 - 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.

AB - 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.

U2 - 10.1186/s13567-020-00798-6

DO - 10.1186/s13567-020-00798-6

M3 - Article

C2 - 32487248

SN - 0928-4249

VL - 51

SP - 75

JO - Veterinary Research

JF - Veterinary Research

IS - 1

ER -

Defining immune correlates during latent and active chlamydial infection in sheep

Abstract / Description of output

Access to Document

Fingerprint

Cite this