Local assessment of the immunohistochemical expression of Foxp3+ regulatory T lymphocytes in the different pathological forms associated with bovine paratuberculosis

Abstract Background Mycobacterium avium subsp. paratuberculosis infected animals show a variety of granulomatous lesions, from focal forms with well-demarcated granulomas restricted to the gut-associated lymphoid tissue (GALT), that are seen in the initial phases or latency stages, to a diffuse gran...

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Main Authors: David Zapico, José Espinosa, Miguel Fernández, Miguel Criado, Noive Arteche-Villasol, Valentín Pérez
Format: Article
Language:English
Published: BMC 2022-08-01
Series:BMC Veterinary Research
Subjects:
Online Access:https://doi.org/10.1186/s12917-022-03399-x
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author David Zapico
José Espinosa
Miguel Fernández
Miguel Criado
Noive Arteche-Villasol
Valentín Pérez
author_facet David Zapico
José Espinosa
Miguel Fernández
Miguel Criado
Noive Arteche-Villasol
Valentín Pérez
author_sort David Zapico
collection DOAJ
description Abstract Background Mycobacterium avium subsp. paratuberculosis infected animals show a variety of granulomatous lesions, from focal forms with well-demarcated granulomas restricted to the gut-associated lymphoid tissue (GALT), that are seen in the initial phases or latency stages, to a diffuse granulomatous enteritis, with abundant (multibacillary) or scant (paucibacillary) bacteria, seen in clinical stages. Factors that determine the response to the infection, responsible for the occurrence of the different types of lesion, are still not fully determined. It has been seen that regulatory T cells (Treg) play an important role in various diseases where they act on the limitation of the immunopathology associated with the immune response. In the case of paratuberculosis (PTB) the role of Treg lymphocytes in the immunity against Map is far away to be completely understood; therefore, several studies addressing this subject have appeared recently. The aim of this work was to assess, by immunohistochemical methods, the presence of Foxp3+ T lymphocytes in intestinal samples with different types of lesions seen in cows with PTB. Methods Intestinal samples of twenty cows showing the different pathological forms of PTB were evaluated: uninfected controls (n = 5), focal lesions (n = 5), diffuse paucibacillary (n = 5) and diffuse multibacillary (n = 5) forms. Foxp3+ lymphocyte distribution was assessed by differential cell count in intestinal lamina propria (LP), gut-associated lymphoid tissue (GALT) and mesenteric lymph node (MLN). Results A significant increase in the number of Foxp3+ T cells was observed in infected animals with respect to control group, regardless of the type of lesion. However, when the different categories of lesion were analyzed independently, all individuals with PTB lesions showed an increase in the amount of Foxp3+ T lymphocytes compared to the control group but this increase was only significant in cows with focal lesions and, to a lesser extent, in animals with diffuse paucibacillary forms. The former showed the highest numbers, significantly different from those found in cows with diffuse lesions, where no differences were noted between the two forms. No specific distribution pattern was observed within the granulomatous lesions in any of the groups. Conclusions The increase of Foxp3+ T cells in focal forms, that have been associated with latency or resistance to infection, suggest an anti-inflammatory action of these cells at these stages, helping to prevent exacerbation of the inflammatory response, as occurs in diffuse forms, responsible for the appearance of clinical signs.
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spelling doaj.art-e1dbe7ad4a814362be41eb3f6229bc3c2022-12-22T02:32:07ZengBMCBMC Veterinary Research1746-61482022-08-0118111110.1186/s12917-022-03399-xLocal assessment of the immunohistochemical expression of Foxp3+ regulatory T lymphocytes in the different pathological forms associated with bovine paratuberculosisDavid Zapico0José Espinosa1Miguel Fernández2Miguel Criado3Noive Arteche-Villasol4Valentín Pérez5Departamento de Sanidad Animal, Facultad de Veterinaria, Instituto de Ganadería de Montaña (CSIC-ULE), Universidad de LeónDepartamento de Sanidad Animal, Facultad de Veterinaria, Instituto de Ganadería de Montaña (CSIC-ULE), Universidad de LeónDepartamento de Sanidad Animal, Facultad de Veterinaria, Instituto de Ganadería de Montaña (CSIC-ULE), Universidad de LeónDepartamento de Sanidad Animal, Facultad de Veterinaria, Instituto de Ganadería de Montaña (CSIC-ULE), Universidad de LeónDepartamento de Sanidad Animal, Facultad de Veterinaria, Instituto de Ganadería de Montaña (CSIC-ULE), Universidad de LeónDepartamento de Sanidad Animal, Facultad de Veterinaria, Instituto de Ganadería de Montaña (CSIC-ULE), Universidad de LeónAbstract Background Mycobacterium avium subsp. paratuberculosis infected animals show a variety of granulomatous lesions, from focal forms with well-demarcated granulomas restricted to the gut-associated lymphoid tissue (GALT), that are seen in the initial phases or latency stages, to a diffuse granulomatous enteritis, with abundant (multibacillary) or scant (paucibacillary) bacteria, seen in clinical stages. Factors that determine the response to the infection, responsible for the occurrence of the different types of lesion, are still not fully determined. It has been seen that regulatory T cells (Treg) play an important role in various diseases where they act on the limitation of the immunopathology associated with the immune response. In the case of paratuberculosis (PTB) the role of Treg lymphocytes in the immunity against Map is far away to be completely understood; therefore, several studies addressing this subject have appeared recently. The aim of this work was to assess, by immunohistochemical methods, the presence of Foxp3+ T lymphocytes in intestinal samples with different types of lesions seen in cows with PTB. Methods Intestinal samples of twenty cows showing the different pathological forms of PTB were evaluated: uninfected controls (n = 5), focal lesions (n = 5), diffuse paucibacillary (n = 5) and diffuse multibacillary (n = 5) forms. Foxp3+ lymphocyte distribution was assessed by differential cell count in intestinal lamina propria (LP), gut-associated lymphoid tissue (GALT) and mesenteric lymph node (MLN). Results A significant increase in the number of Foxp3+ T cells was observed in infected animals with respect to control group, regardless of the type of lesion. However, when the different categories of lesion were analyzed independently, all individuals with PTB lesions showed an increase in the amount of Foxp3+ T lymphocytes compared to the control group but this increase was only significant in cows with focal lesions and, to a lesser extent, in animals with diffuse paucibacillary forms. The former showed the highest numbers, significantly different from those found in cows with diffuse lesions, where no differences were noted between the two forms. No specific distribution pattern was observed within the granulomatous lesions in any of the groups. Conclusions The increase of Foxp3+ T cells in focal forms, that have been associated with latency or resistance to infection, suggest an anti-inflammatory action of these cells at these stages, helping to prevent exacerbation of the inflammatory response, as occurs in diffuse forms, responsible for the appearance of clinical signs.https://doi.org/10.1186/s12917-022-03399-xMycobacterium avium subsp, paratuberculosisFoxp3+intestinal tissuetype of lesionregulatory T lymphocytescattle
spellingShingle David Zapico
José Espinosa
Miguel Fernández
Miguel Criado
Noive Arteche-Villasol
Valentín Pérez
Local assessment of the immunohistochemical expression of Foxp3+ regulatory T lymphocytes in the different pathological forms associated with bovine paratuberculosis
BMC Veterinary Research
Mycobacterium avium subsp, paratuberculosis
Foxp3+
intestinal tissue
type of lesion
regulatory T lymphocytes
cattle
title Local assessment of the immunohistochemical expression of Foxp3+ regulatory T lymphocytes in the different pathological forms associated with bovine paratuberculosis
title_full Local assessment of the immunohistochemical expression of Foxp3+ regulatory T lymphocytes in the different pathological forms associated with bovine paratuberculosis
title_fullStr Local assessment of the immunohistochemical expression of Foxp3+ regulatory T lymphocytes in the different pathological forms associated with bovine paratuberculosis
title_full_unstemmed Local assessment of the immunohistochemical expression of Foxp3+ regulatory T lymphocytes in the different pathological forms associated with bovine paratuberculosis
title_short Local assessment of the immunohistochemical expression of Foxp3+ regulatory T lymphocytes in the different pathological forms associated with bovine paratuberculosis
title_sort local assessment of the immunohistochemical expression of foxp3 regulatory t lymphocytes in the different pathological forms associated with bovine paratuberculosis
topic Mycobacterium avium subsp, paratuberculosis
Foxp3+
intestinal tissue
type of lesion
regulatory T lymphocytes
cattle
url https://doi.org/10.1186/s12917-022-03399-x
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