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Apoptosis levels in bovine Johne's disease ileal lesions and association with bacterial numbers.

ABSTRACT: Johne's disease (JD) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP). While it is generally accepted that MAP employs immune subversion mechanisms, aspects of the host-pathogen relationship are not fully understood. We sampled 3 ileal tissue sections from 17 naturally infected cattle (n = 51 sections) to analyze differences in cell types, apoptosis, and phagocytic cells. Diffuse multibacillary (DM) was the most common lesion type (n = 17) followed by diffuse intermediate (DI; n = 15). DM lesions had significantly greater proportion of Treg cells (CD3⁺ FoxP3⁺⁾ relative to all CD3⁺ T cells as compared to DI forms (P < .05). CD68⁺ individual cell size was significantly smaller in DM than in diffuse lymphocytic (DL) forms (P < .05). Area of caspase-3 positivity (apoptosis) was greater in DM lesions than DL (P < .05) and DI (P < .0001), and was linked to higher numbers of MAP within the macrophage.

SUBMITTER: Lucena AN

PROVIDER: S-EPMC8581713 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Apoptosis levels in bovine Johne's disease ileal lesions and association with bacterial numbers.

Lucena Amalia Naranjo- AN Garza-Cuartero Laura L McAloon Conor C Mulcahy Grace G Zintl Annetta A Perez José J Wolfe Alan A

Veterinary pathology 20210630 6

Johne's disease (JD) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP). While it is generally accepted that MAP employs immune subversion mechanisms, aspects of the host-pathogen relationship are not fully understood. We sampled 3 ileal tissue sections from 17 naturally infected cattle (n = 51 sections) to analyze differences in cell types, apoptosis, and phagocytic cells. Diffuse multibacillary (DM) was the most common lesion t ...[more]

PMID: 34190009

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Project description:Mycobacterium avium subsp. paratuberculosis (MAP), the etiological agent of Johne's disease (JD) in ruminants, establishes a prolonged and often lifelong enteric infection. The implementation of control measures for bovine JD has faced obstacles due to the considerable expenses involved in disease surveillance and hindered by unreliable and inadequate diagnostic tests, emphasizing the need for an effective vaccine that can stimulate mucosal immunity in the gastrointestinal tract. Previous investigations have demonstrated that deletion of the BacA gene in MAP produces an attenuated strain that can transiently colonize the calf small intestine while retaining its capacity to stimulate systemic immune responses similar to wildtype MAP strains. This study assessed the efficacy of the BacA gene deletion MAP strain, referred to as the BacA vaccine, when administered orally to young calves. The research aimed to evaluate its effectiveness in controlling MAP intestinal infection and to investigate the immune responses elicited by mucosal vaccination. The study represents the first evaluation of an enteric modified live MAP vaccine in the context of an oral MAP challenge in young calves. Oral immunization with BacA reduced MAP colonization specifically in the ileum and ileocecal valve. This partially protective immune response was associated with an increased frequency of CD4+ and CD8+ T cells with a pro-inflammatory phenotype (IFNγ+/TNFα+) in vaccinated animals. Moreover, re-stimulated PBMCs from vaccinated animals showed increased expression of IFNγ, IP-10, IL-2, and IL-17 at 10- and 12-weeks post challenge. Furthermore, immunophenotyping of blood leukocytes revealed that vaccinated calves had increased levels of T cells expressing cell-surface markers consistent with long-term central memory. Overall, our findings provide new insights into the development and immunogenicity of a modified live MAP vaccine against bovine JD, demonstrating oral vaccination can stimulate host immune responses that can be protective against enteric MAP infection.

Dataset Information

Apoptosis levels in bovine Johne's disease ileal lesions and association with bacterial numbers.

Publications

Apoptosis levels in bovine Johne's disease ileal lesions and association with bacterial numbers.

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