Apoptosis of lymph node and peripheral blood cells in ovine Johne's disease
Kumudika de Silva1, Sally Browne, Douglas J Begg
1Faculty of Veterinary Science, University of Sydney, 425 Werombi Road, Camden, NSW 2570, Australia.
Abstract:
Ovine Johne's disease (OJD) is a degenerative wasting condition of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Similar to other pathogenic mycobacterial infections it is a slow-progressing chronic disease and subclinically infected individuals can spread the disease while appearing healthy. MAP infects macrophages and the host responds by mounting a cell-mediated immune response. Disease progression is associated with immune dysfunction but the reasons are unknown. Increasing our current knowledge of the immunological mechanisms involved in disease progression, including apoptotic responses, may allow advancements in the area of early diagnosis, identification of resistant animals and disease control. We describe lymphocyte apoptosis in peripheral blood mononuclear cells (PBMC) and lymph node cells from sheep exposed to MAP as well as from healthy non-exposed sheep. Apoptosis in intestinal lymph node cells from MAP-exposed infected sheep, but not in MAP-exposed uninfected sheep, increased in response to MAP antigen. In this first longitudinal study of lymphocyte apoptosis using an experimental infection model of MAP infection, we found that there was a transient increase of ex vivo PBMC apoptosis in MAP-exposed sheep soon after exposure to MAP (4 months post inoculation). MAP antigen-specific apoptosis occurred later, at 12 months post inoculation. The cells involved were mainly γδ and CD4(+) T cells. Antigen-mediated lymphocyte apoptosis during mycobacterial disease progression could contribute to the immune dysfunction in Johne's disease.
Insights
Ovine Johne's disease (OJD) involves lymphocyte apoptosis, a programmed cell death. This study tracked apoptosis in sheep experimentally infected with Mycobacterium avium subsp. paratuberculosis (MAP), revealing antigen-specific cell death in later stages.
Area of Science:
- Immunology
- Veterinary Medicine
- Microbiology
Background:
- Ovine Johne's disease (OJD) is a chronic wasting condition in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP).
- Disease progression is linked to immune dysfunction, with underlying immunological mechanisms, including apoptosis, remaining unclear.
- Understanding lymphocyte apoptosis in OJD can aid early diagnosis, identification of resistant animals, and disease control strategies.
Purpose of the Study:
- To investigate lymphocyte apoptosis in sheep experimentally infected with MAP.
- To determine the kinetics and cell types involved in MAP antigen-specific apoptosis during OJD progression.
Main Methods:
- Longitudinal study of lymphocyte apoptosis in peripheral blood mononuclear cells (PBMC) and lymph node cells from MAP-exposed and control sheep.
- Measurement of ex vivo PBMC apoptosis and MAP antigen-specific apoptosis at various time points post-inoculation.
- Identification of lymphocyte subsets (e.g., γδ and CD4(+) T cells) undergoing apoptosis.
Main Results:
- A transient increase in ex vivo PBMC apoptosis was observed in MAP-exposed sheep at 4 months post-inoculation.
- MAP antigen-specific lymphocyte apoptosis occurred later, at 12 months post-inoculation, primarily involving γδ and CD4(+) T cells.
- Intestinal lymph node cells from infected sheep showed increased apoptosis in response to MAP antigen.
Conclusions:
- Antigen-mediated lymphocyte apoptosis is a feature of Ovine Johne's disease progression in sheep.
- This apoptosis, particularly in γδ and CD4(+) T cells, may contribute to the immune dysfunction observed in MAP-infected animals.
- The findings provide insights into the immunological mechanisms of OJD and potential targets for intervention.
Related Concept Videos
Apoptosis
Secondary Lymphoid Organs
The spleen is a vital organ in the lymphatic system, nestled in the upper left side of the abdomen. It is composed of two primary regions: the red pulp and the white pulp, each having distinct functions. The red pulp performs a significant role in blood filtration. It efficiently purges the blood of old or damaged red blood cells and...
Lymphoid Cells and Tissues
Lymphoid cells consist of various types of immune system cells. These include B and T lymphocytes, which are responsible for producing antibodies and killing infected cells, respectively. Dendritic cells act as messengers between the innate and adaptive...
Primary Lymphoid Organs
The red bone marrow is a soft, spongy tissue nestled in the interior of long bones such as the humerus and femur. It is the site...
Detailed Structure and Function of Lymph Nodes
From a histological perspective, lymph nodes can be split into two main areas: the superficial cortex and the deep medulla. The outer cortex is populated by dendritic cells, macrophages, and B lymphocytes, which are densely packed into follicles. When these B-lymphocytes are presented...
The Intrinsic Apoptotic Pathway


