Summary Tuberculosis most commonly presents as a pulmonary disease, in which infection, persistence, and induction of transmissible pathology all occur in the lungs. If viewed as a pulmonary disease, ...enlarged lymph nodes represent reactive adenitis, and extrapulmonary forms of tuberculosis (including lymphatic tuberculosis) are not transmissible, hence representing an evolutionary dead-end for the pathogen. In an alternative theory, Mycobacterium tuberculosis passes asymptomatically through the lungs and rapidly establishes a chronic lymphatic infection. After a period of weeks to decades secondary lung pathology develops, ultimately allowing transmission to occur. Evidence that supports this lymphatic model includes historical descriptions of human tuberculosis from the preantibiotic era, analogy with other mycobacterial infections, observations of tuberculosis in non-human hosts, and experimental models of tuberculosis disease. At a fundamental level, a lymphocentric model proposes that spread of organisms outside the lung parenchyma is essential to induce adaptive immunity, which is crucial for the generation of transmissible pathology. Furthermore, a lymphatic model could explain why the lesion associated with primary infection (Ghon focus) is anatomically separated from the most common site of reactivation disease (the apex). More practically, an alternative perspective that classes tuberculosis as a lymphatic disease might affect strategies for preclinical and clinical assessment of novel diagnostics, drugs, and vaccines.
γδ T cells contribute uniquely to immune competence. Nevertheless, how they function remains an enigma. It is unclear what most γδ T cells recognize, what is required for them to mount an immune ...response, and how the γδ T cell response is integrated into host immune defense. Here, we report that a noted B cell antigen, the algae protein phycoerythrin (PE), is a murine and human γδ T cell antigen. Employing this specificity, we demonstrated that antigen recognition activated naive γδ T cells to make interleukin-17 and respond to cytokine signals that perpetuate the response. High frequencies of antigen-specific γδ T cells in naive animals and their ability to mount effector response without extensive clonal expansion allow γδ T cells to initiate a swift, substantial response. These results underscore the adaptability of lymphocyte antigen receptors and suggest an antigen-driven rapid response in protective immunity prior to the maturation of classical adaptive immunity.
► Murine and human γδ T cells recognize a microbial encoded B cell antigen ► Naive γδ T cells develop into IL-17 effectors in response to this antigen ► Antigen-activated γδ T cells gain the ability to respond to cytokine signals ► Robust and sustained IL-17 production requires both TCR and cytokine signals
We challenged reindeer by the intracranial route with the agent of chronic wasting disease sourced from white-tailed deer, mule deer, or elk and tested for horizontal transmission to naive reindeer. ...Reindeer were susceptible to chronic wasting disease regardless of source species. Horizontal transmission occurred through direct contact or indirectly through the environment.
Celotno besedilo
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bovine tuberculosis (TB) control programs generally rely on the tuberculin skin test (TST) for ante-mortem detection of Mycobacterium bovis-infected cattle.
Present findings demonstrate that a rapid ...antibody test based on Dual-Path Platform (DPP
) technology, when applied 1-3 weeks after TST, detected 9 of 11 and 34 of 52 TST non-reactive yet M. bovis-infected cattle from the US and GB, respectively. The specificity of the assay ranged from 98.9% (n = 92, US) to 96.0% (n = 50, GB) with samples from TB-free herds. Multi-antigen print immunoassay (MAPIA) revealed the presence of antibodies to multiple antigens of M. bovis in sera from TST non-reactors diagnosed with TB.
Thus, use of serologic assays in series with TST can identify a significant number of TST non-reactive tuberculous cattle for more efficient removal from TB-affected herds.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•This is the first study to demonstrate IgM and IgG antibody responses to defined mycobacterial antigens in European bison (Bison bonasus) naturally infected with Mycobacterium caprae.•Antibody ...responses to M. caprae infection in European bison included IgM antibodies against MPB70/MPB83 and IgG antibodies to both MPB70/MPB83 and CFP10/ESAT-6.•Antibodies were not detected in non-infected European bison or in animals infected with Mycobacterium avium or Mycobacterium xenopi.•Serodiagnostic assays may prove useful for tuberculosis surveillance in free-ranging and captive (e.g., in zoos and breeding centers) European bison.
Mycobacterium caprae, a member of the Mycobacterium tuberculosis complex, infects humans and animals causing lesions and disease like that of Mycobacterium bovis. The aim of this study was to evaluate antibody responses in European Bison (EB, Bison bonasus; a vulnerable species) naturally infected with M. caprae using dual path platform (DPP) BovidTB test and multi-antigen print immunoassay (MAPIA). Study cohorts consisted of naturally M. caprae-infected EB (n = 4), M. caprae-exposed but uninfected (n = 3), EB infected with non-tuberculous mycobacteria or other respiratory pathogens (n = 3), and negative controls (n = 19). M. caprae-infected EB were seropositive by both DPP and MAPIA; 3/4 were seropositive by DPP; and 4/4 were seropositive by MAPIA. One M. caprae-infected animal that developed generalized disease with most advanced gross lesions in the group produced the most robust antibody response. All 25 EB with no culture-confirmed M. caprae infection, including three animals exposed to M. caprae and three other animals infected with non-tuberculous pathogens, were seronegative on both tests. Antibody responses to M. caprae infection included IgM antibodies against MPB70/MPB83 and IgG antibodies to both MPB70/MPB83 and CFP10/ESAT-6. This study demonstrates the potential for use of serological assays in the ante-mortem diagnosis of M. caprae infection in EB.
Highlights ► BCG is particularly protective when administered to neonatal calves. ► Subunit vaccines may be used to boost immunity in cattle. ► T cell central memory responses correlate with ...protection to M. bovis challenge. ► DIVA approaches are feasible in cattle using in vitro or in vivo methods. ► BCG is being considered for use in several wildlife reservoirs of M. bovis.
Biomarkers of cell-mediated immunity to bovine tuberculosis Palmer, Mitchell V.; Thacker, Tyler C.; Rabideau, Meaghan M. ...
Veterinary immunology and immunopathology,
February 2020, 2020-Feb, 2020-02-00, 20200201, Letnik:
220
Journal Article
Recenzirano
Odprti dostop
•Messenger RNA for IFN-γ, TNF-α and other key cytokines were significantly upregulated in M. bovis infected animals compared to non-infected.•Differential expression of IFN-γ, CXCL9, CXCL10, IL-21 ...and IL-13 as early as 2 weeks after infection of calves with M. boviswas seen.•CXCL9 protein was specifically produced in whole blood from M. bovis infected animals when stimulated with PPDb or specific proteins.•CXCL10 protein was found in significant quantities in the serum of infected and uninfected animals.
Whole blood based assays, particularly interferon gamma (IFN-γ) release assays (IGRAs), are used for the diagnosis of both bovine and human tuberculosis (TB). The aim of the current study was to evaluate a panel of cytokines and chemokines for potential use as diagnostic readouts indicative of Mycobacterium bovis (M. bovis) infection in cattle. A gene expression assay was used to determine the kinetics of the response to M. bovis purified protein derivative and a fusion protein consisting of ESAT-6, CFP10, and Rv3615c upon aerosol infection with ∼104 cfu of M. bovis. The panel of biomarkers included: IFN-γ, CXCL9, CXCL10, CCL2, CCL3, TNF-α, IL-1α, IL-1β, IL-1Ra, IL-22, IL-21 and IL-13. Protein levels of IFN-γ, CXCL9, and CXCL10 were determined by ELISA. Findings suggest that CXCL9, CXCL10, IL-21, IL-13, and several acute phase cytokines may be worth pursuing as diagnostic biomarkers of M. bovis infection in cattle.
Mycobacterium bovis, the causative agent of bovine tuberculosis, is a pathogen that impacts both animal and human health. Consequently, there is a need to improve understanding of disease dynamics, ...identification of infected animals, and characterization of the basis of immune protection. This study assessed the transcriptional changes occurring in cattle during the early weeks following a M. bovis infection. RNA-seq analysis of whole blood-cell transcriptomes revealed two distinct transcriptional clusters of infected cattle at both 4- and 10-weeks post-infection that correlated with disease severity. Cattle exhibiting more severe disease were transcriptionally divergent from uninfected animals. At 4-weeks post-infection, 25 genes had commonly increased expression in infected cattle compared to uninfected cattle regardless of disease severity. Ten weeks post-infection, differential gene expression was only observed when severely-affected cattle were compared to uninfected cattle. This indicates a transcriptional divergence based on clinical status following infection. In cattle with more severe disease, biological processes and cell type enrichment analyses revealed overrepresentation of innate immune-related processes and cell types in infected animals. Collectively, our findings demonstrate two distinct transcriptional profiles occur in cattle following M. bovis infection, which correlate to clinical status.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The hallmark lesion of tuberculosis in humans and animals is the granuloma. The granuloma represents a distinct host cellular immune response composed of epithelioid macrophages, lymphocytes, and ...multinucleated giant cells, often surrounding a caseous necrotic core. Within the granuloma, host-pathogen interactions determine disease outcome. Factors within the granulomas such as cytokines and chemokines drive cell recruitment, activity, function and ultimately the success or failure of the host's ability to control infection. Hence, an understanding of the granuloma-level cytokine response is necessary to understand tuberculosis pathogenesis. In-situ cytokine expression patterns were measured using a novel in situ hybridization assay, known as RNAScope® in granulomas of the lungs, tracheobronchial lymph nodes and caudal mediastinal lymph nodes of cattle experimentally infected with Mycobacterium bovis via aerosol exposure. In spite of microscopic morphological similarities, significant differences were seen between late stage granulomas of the lung compared to those of the tracheobronchial lymph nodes for IL-17A, IFN-γ, TGF-β, IL10 and IL-22 but not for TNF-α. Additionally, significant differences were noted between granulomas from two different thoracic lymph nodes that both receive afferent lymphatics from the lungs (i.e., tracheobronchial and caudal mediastinal lymph nodes) for TNF-α, IL-17A, IFN-γ, TGF-β and IL-10 but not for IL-22. These findings show that granuloma morphology alone is not a reliable indicator of granuloma function as granulomas of similar morphologies can have disparate cytokine expression patterns. Moreover, anatomically distinct lymph nodes (tracheobronchial vs caudal mediastinal) differ in cytokine expression patterns even when both receive afferent lymphatics from a lung containing tuberculoid granulomas. These findings show that selection of tissue and anatomic location are critical factors in assessing host immune response to M. bovis and should be considered carefully.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Antibody responses in animal tuberculosis are characterized by distinct antigen reactivity profiles in various host species.•MPB83 proteins is predominantly recognized in cattle and fallow deer, ...CFP10/ESAT-6 is mostly reactive in elephants, whereas elk and white-tailed deer produce antibodies to these two antigens at similar rates.•Further analyses of predominant antigen recognition in various host species will improve the accuracy of immunodiagnostic tests for tuberculosis.
Using multi-antigen print immunoassay and DPP® VetTB Assay approved in the United States for testing captive cervids and elephants, we analyzed antibody recognition of MPB83 and CFP10/ESAT-6 antigens in Asian elephants (Elephas maximus) infected with Mycobacterium tuberculosis and in white-tailed deer (Odocoileus virginianus), fallow deer (Dama dama), elk (Cervus elaphus), and cattle (Bos taurus) infected with Mycobacterium bovis. Serum IgG reactivity to MPB83 was found in the vast majority of tuberculous cattle and cervid species among which white-tailed deer and elk also showed significant CFP10/ESAT-6 recognition rates with added serodiagnostic value. In contrast, the infected elephants developed antibody responses mainly to CFP10/ESAT-6 with MPB83 reactivity being relatively low. The findings demonstrate distinct patterns of predominant antigen recognition by different animal hosts in tuberculosis.
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