Biomarkers for Detecting Resilience against Mycobacterial Disease in Animals

Abstract

Paratuberculosis and bovine tuberculosis are two mycobacterial diseases of ruminants which have a considerable impact on livestock health, welfare, and production. These are chronic “iceberg” diseases which take years to manifest and in which many subclinical cases remain undetected. Suggested biomarkers to detect infected or diseased animals are numerous and include cytokines, peptides, and expression of specific genes; however, these do not provide a strong correlation to disease. Despite these advances, disease detection still relies heavily on dated methods such as detection of pathogen shedding, skin tests, or serology. Here we review the evidence for suitable biomarkers and their mechanisms of action, with a focus on identifying animals that are resilient to disease. A better understanding of these factors will help establish new strategies to control the spread of these diseases.

Early Detection of Mycobacterium avium subsp. paratuberculosis Infected Cattle: Use of Experimental Johnins and Innovative Interferon-Gamma Test Interpretative Criteria

“…However, the humoral immune response, detectable by ELISA, appears only in the late stage when the disease is clinically manifested (60). The animals become infected at a young age, but the clinical PTB form does not occur until 2-3 years, probably because of the control role of innate and CMI, genetic susceptibility of the animal, and environmental factors (45,47,48,50,75). Therefore, it is strategically advantageous to decide in which categories include animals with a positive reaction to the IFN-γ test and tested negative to traditional tests for MAP infection diagnosis (49,75).…”

“…Conversely, in a herd with a high prevalence of PTB, animals with a positive reaction to the IFN-γ test for MAP infection diagnosis might be at risk of MAP shedding, and therefore, animals need to be checked more often than others. As reported by several authors (49,75), these cattle could also include the animals able to contain the evolution of the MAP infection, without ever developing the subclinical and clinical forms of PTB, and therefore, they represent a genetic resource to be preserved and enhanced.…”

MicroRNAs as Biomarkers for Animal Health and Welfare in Livestock

“…This review aimed to describe and critically assess the relevant current literature regarding these challenging events, giving only a brief overview of miRNAs involved in immune responses induced by infectious diseases. Despite the increased interest in investigating miRNAs involved in veterinary-relevant infectious diseases in the past few years, this topic is not within the main scope of this review, and has been described in excellent recent reports (19,20,25,(40)(41)(42)(43)(44) Table 3).…”

“…A recent review defined miRNAs as key regulators of host gene expression and immune defenses, as well as promising biomarkers for resistance to mycobacterial infection (20). In cattle, many miRNAs have been reported to be modulated during mycobacterial infections (47-51).…”

“…Other studies have aimed to identify hormones and other molecules that are quantified at levels out of a "physiological range" (15)(16)(17). miRNAs are fine-tuning coordinators of cellular processes, including the modulation of animal development, homeostasis, immune responses, and control of infection, and are also crucial for the regulation of stem cell self-renewal and tissue differentiation (18)(19)(20)(21). Following a physiological stimulus or injury, circulating miRNAs (c-miRNAs) can be released from cells into the blood or other body fluids in either an active (secretion) or passive (membrane leaking) manner (22)(23)(24).…”