Can Immune Response Mechanisms Explain the Fecal Shedding Patterns of Cattle Infected with Mycobacterium avium Subspecies paratuberculosis?
Author(s)
Magombedze, G
Eda, S
Koets, A
Type
Journal Article
Abstract
Johne’s disease (JD) is a chronic disease in ruminants and is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). At late stages of the disease, MAP bacilli are shed via feces excretion and in turn create the potential for oral-fecal transmission. The role of the host immune response in MAP bacteria shedding patterns at different stages of JD is still unclear. We employed mathematical modeling to predict if the variation in MAP shedding could be correlated to the immune response in infected animals. We used a novel inverse modeling approach that assumed biological interactions among the antigen-specific lymphocyte proliferation response (cell-mediated response), antibody/humoral immune responses, and MAP bacteria. The modeling framework was used to predict and test possible biological interactions between the measured variables and returns only the essential interactions that are relevant in explaining the observed cattle MAP experimental infection data. Through confronting the models with data, we predicted observed effects (enhancement or suppression) and extents of interactions among the three variables. This analysis enabled classification of the infected cattle into three different groups that correspond to the unique predicted immune responses that are essential to explain the data from cattle within these groups. Our analysis highlights the strong and weak points of the modeling approach, as well as the key immune mechanisms predicted to be expressed in all animals and those that were different between animals, hence giving insight into how animals exhibit different disease dynamics and bacteria shedding patterns.
Date Issued
2016-01-25
Date Acceptance
2015-12-21
Citation
PLOS One, 2016, 11 (1)
ISSN
1932-6203
Publisher
Public Library of Science
Journal / Book Title
PLOS One
Volume
11
Issue
1
Copyright Statement
© 2016 Magombedze et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
BLOOD MONONUCLEAR-CELLS
PERIPHERAL-BLOOD
GAMMA-INTERFERON
JOHNES-DISEASE
MACROPHAGES
INTERLEUKIN-10
EXPRESSION
SURVIVAL
CULTURE
CALVES
Animals
Bacterial Shedding
Cattle
Cattle Diseases
Feces
Mycobacterium avium subsp. paratuberculosis
Paratuberculosis
General Science & Technology
MD Multidisciplinary
Publication Status
Published
Article Number
e0146844