Interleukin 8 and Pentaxin (C-Reactive Protein) as Potential New Biomarkers of Bovine Tuberculosis

Gao, Xintao; Guo, Xiaoyu; Li, Ming; Ji, Hong; Lin, Weidong; Fang, Lichun; Jiang, Yao; Zhu, Hongfei; Zhang, Zhifang; Ding, Jiabo; Xin, Ting

doi:10.1128/jcm.00274-19

Cited by 23 publications

(25 citation statements)

References 38 publications

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“…World Health Organization pointed out that human TB can only be controlled by eradicating bTB (22). An efficient way to eradicate bTB is to slaughter M. bovis-infected cattle, and prioritizing the slaughter of bTB cattle that actively shed mycobacteria was recommended (23). An even more urgent need is to reveal the immune heterogeneity of bTB in different stages, and to develop and apply improved diagnostic techniques for active bTB to prevent them from transmitting bTB.…”

Section: Discussionmentioning

confidence: 99%

Potential Diagnostic Value of the Peripheral Blood Mononuclear Cell Transcriptome From Cattle With Bovine Tuberculosis

Fang

Lin

et al. 2020

Front. Vet. Sci.

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Bovine tuberculosis (bTB) is a chronic disease of cattle caused by Mycobacterium bovis. During early-stage infection, M. bovis-infected cattle shed mycobacteria through nasal secretions, which can be detected via nested-polymerase chain reaction (PCR) experiments. Little research has focused on immune responses in nested PCR-positive (bTB PCR-P) or nested PCR-negative (bTB PCR-N) M. bovis-infected cattle. Here, we investigated the transcriptomes of peripheral blood mononuclear cells (PBMCs), with or without stimulation by purified protein derivative of bovine tuberculin (PPD-B), among bTB PCR-P, bTB PCR-N, and healthy cattle using RNA-Seq. We also explored the potential value of PBMC transcripts as novel biomarkers for diagnosing bTB. Numerous differentially expressed genes were identified following pair-wise comparison of different groups, with or without PPD-B stimulation (adjusted p < 0.05). Compared with healthy cattle, bTB PCR-P, and bTB PCR-N cattle shared 5 significantly dysregulated biological pathways, including Cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, Hematopoietic cell lineage, Osteoclast differentiation and HTLV-I infection. Notably, dysregulated biological pathways of bTB PCR-P and bTB PCR-N cattle were associated with cell death and phagocytosis, respectively. Lymphotoxin alpha and interleukin-8 could potentially differentiate M. bovis-infected and healthy cattle upon stimulation with PPD-B, with area-under-the-curve (AUC) values of 0.9991 and 0.9343, respectively. B cell lymphoma 2 and chitinase 3-like 1 might enable differentiation between bTB PCR-P and bTB PCR-N upon stimulation with PPD-B, with AUC values of 0.9100 and 0.8893, respectively. Thus, the PBMC transcriptome revealed the immune responses in M. bovis-infected cattle (bTB PCR-P and bTB PCR-N) and may provide a novel sight in bTB diagnosis.

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Section: Discussionmentioning

confidence: 99%

Potential Diagnostic Value of the Peripheral Blood Mononuclear Cell Transcriptome From Cattle With Bovine Tuberculosis

Fang

Lin

et al. 2020

Front. Vet. Sci.

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“…The permanence of neutrophils at the site of injury depends on the production of chemical mediators, such as TNF-α [ 44 ]. Nonetheless, recent studies associate it mostly with interleukin-8 (IL8) [ 45 ], a potential marker for M. bovis infections [ 46 ]. Neutrophils arrive in two “waves”, the first relates to the innate response against the pathogen and the second to the adaptive response [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Isolation and Histopathological Changes Associated with Non-Tuberculous Mycobacteria in Lymph Nodes Condemned at a Bovine Slaughterhouse

Hernández-Jarguín

Martı́nez-Burnes

Molina-Salinas

et al. 2020

Veterinary Sciences

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Background: non-tuberculous mycobacteria (NTM) infect humans and animals and have a critical confounding effect on the diagnosis of bovine tuberculosis. The Official Mexican Standard (Norma Oficial Mexicana, NOM-ZOO-031-1995) for food safety regulates Mycobacterium bovis in cattle, but not the NTM species. The study’s objective was to isolate and identify the NTM present in condemned bovine lymph nodes in a slaughterhouse, characterize the histological lesions, and correlate bacteriological and microscopic findings with the antemortem tuberculin skin test. Methods: from 528 cattle, one or two pooled samples of lymph nodes from each animal were cultured for Mycobacteria spp. and processed for histopathology. Results: mycobacteria were isolated from 54/528 (10.2%) of the condemned lymph nodes; 25/54 (46.2%) of these isolates were NTM; 4 bacteriological cultures with fungal contamination were discarded. Granulomatous and pyogranulomatous inflammation were present in 6/21 (28.6%) and 7/21 (33.3%) of the NTM-positive lymph nodes, respectively. The species of NTM associated with granulomatous lymphadenitis were M. scrofulaceum, M. triviale, M. terrae, and M. szulgai, while those causing pyogranulomatous lesions were M. szulgai, M. kansasii, M. phlei, and M. scrofulaceum. Conclusions: the NTM infections can cause false-positive results in the tuberculin test because of cross immune reactivity and interference with the postmortem identification of M. bovis in cattle.

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“…Several promising cytokine/chemokine biomarkers of M. bovis infection and disease in domestic and wildlife species have been revealed in recent years, in addition to the widely recognized host biomarker IFN-γ. These include, although are not limited to, IP-10, IL-1β, IL-4, IL-8, IL-17A, CXCL9, IL-10, and IL-22 (37,40,(78)(79)(80)(81)(82)(83)(84). Both protein and gene expression assays have been used to assess biomarker levels in different species and have facilitated identification of additional targets for diagnostic development (5).…”

Section: Cytokine/chemokine Biomarkers Of Mycobacterium Bovis Infectionmentioning

confidence: 99%

“…The precise role of the chemokine IL-8 in TB has not been fully elucidated, although studies have demonstrated IL-8 binding to tubercle bacilli and interactions with the pathogen that appear to enhance mycobactericidal characteristics of macrophages and neutrophils (131). Increased IL-8 is also required for granuloma formation (84). (39).…”

Section: Il-8mentioning

confidence: 99%

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

et al. 2021

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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.

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Interleukin 8 and Pentaxin (C-Reactive Protein) as Potential New Biomarkers of Bovine Tuberculosis

Cited by 23 publications

References 38 publications

Potential Diagnostic Value of the Peripheral Blood Mononuclear Cell Transcriptome From Cattle With Bovine Tuberculosis

Potential Diagnostic Value of the Peripheral Blood Mononuclear Cell Transcriptome From Cattle With Bovine Tuberculosis

Isolation and Histopathological Changes Associated with Non-Tuberculous Mycobacteria in Lymph Nodes Condemned at a Bovine Slaughterhouse

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

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