Cell-Mediated Immunological Biomarkers and Their Diagnostic Application in Livestock and Wildlife Infected With Mycobacterium bovis

Abstract

Mycobacterium bovis has the largest host range of the Mycobacterium tuberculosis complex and infects domestic animal species, wildlife, and humans. The presence of global wildlife maintenance hosts complicates bovine tuberculosis (bTB) control efforts and further threatens livestock and wildlife-related industries. Thus, it is imperative that early and accurate detection of M. bovis in all affected animal species is achieved. Further, an improved understanding of the complex species-specific host immune responses to M. bovis could enable the development of diagnostic tests that not only identify infected animals but distinguish between infection and active disease. The primary bTB screening standard worldwide remains the tuberculin skin test (TST) that presents several test performance and logistical limitations. Hence additional tests are used, most commonly an interferon-gamma (IFN-γ) release assay (IGRA) that, similar to the TST, measures a cell-mediated immune (CMI) response to M. bovis. There are various cytokines and chemokines, in addition to IFN-γ, involved in the CMI component of host adaptive immunity. Due to the dominance of CMI-based responses to mycobacterial infection, cytokine and chemokine biomarkers have become a focus for diagnostic tests in livestock and wildlife. Therefore, this review describes the current understanding of host immune responses to M. bovis as it pertains to the development of diagnostic tools using CMI-based biomarkers in both gene expression and protein release assays, and their limitations. Although the study of CMI biomarkers has advanced fundamental understanding of the complex host-M. bovis interplay and bTB progression, resulting in development of several promising diagnostic assays, most of this research remains limited to cattle. Considering differences in host susceptibility, transmission and immune responses, and the wide variety of M. bovis-affected animal species, knowledge gaps continue to pose some of the biggest challenges to the improvement of M. bovis and bTB diagnosis.

Bacterial Ghosts of Pseudomonas aeruginosa as a Promising Candidate Vaccine and Its Application in Diabetic Rats

“…These results suggest the successful elicitation of both humoral and cell-mediated immune responses. Supporting our finding, an interferon-gamma (IFN-) release assay (IGRA) is used to assess a cell-mediated immune (CMI) response to Mycobacterium bovis, comparable to the tuberculin skin test [27]. Consequently, we used a rat diabetic ulcer model to evaluate PAGs vaccine efficacy.…”

Epidemiology ofMycobacterium bovisinfection in free-ranging rhinoceros in Kruger National Park, South Africa

“…Importantly, there is a potential for misclassification of M. bovis infection status, due to the sole reliance on this single available diagnostic platform. The IGRA is a standard method for diagnosis of active and latent Mycobacterium tuberculosis infection in humans ( 55 , 56 ), and for active M. tuberculosis complex (MTBC) infection in animals ( 25 , 57 ), including rhinoceros ( 4 , 5 , 21 , 52 ). A limitation of this test is that it may not always detect cases of recently acquired infection ( 52 ).…”

“…It is therefore critical to be able to assess infection status in these populations. Recent advances in the development of diagnostic tests ( 12 , 25 ) for M. bovis infection in wildlife beyond conventional mycobacterial culture and M. bovis species confirmation has allowed for antemortem testing. The QuantiFERON TB Gold In-Tube Plus (QFT) (Qiagen)–interferon gamma release assay (QFT–IGRA) was recently validated for use in white rhinoceros ( 4 ), and has been used for testing KNP rhinoceros for M. bovis infection.…”

Comparison of interferon gamma release assay and CXCL9 gene expression assay for the detection of Mycobacterium bovis infection in African lions (Panthera leo)

“…Cytokine assays are widely used for TB diagnosis (Pollock et al, 2013;Bernitz et al, 2021). Antigen-specific IFN-g is the most widely recognized biomarker of M. bovis infection in veterinary studies (Smith et al, 2021b) as well as for M. tuberculosis infection in people (Klautau et al, 2018;Goletti et al, 2022). Studies in humans and cattle have also shown that CXCL9, also known as monokine induced by gamma interferon (MIG), has potential value as a biomarker for TB diagnosis and monitoring (Chung et al, 2015;Kumar et al, 2019;Palmer et al, 2020).…”