Differential Cell Composition and Cytokine Expression Within Lymph Node Granulomas from BCG-Vaccinated and Non-vaccinated Cattle Experimentally Infected with <i>Mycobacterium bovis</i>

Salguero, Francisco J.; Gibson, Susan V.; García-Jiménez, Waldo L.; Gough, Julie E.; Strickland, T.S.; Vordermeier, H. M.; Villarreal‐Ramos, Bernardo

doi:10.1111/tbed.12561

Cited by 33 publications

(59 citation statements)

References 42 publications

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“…This may be due to the fact that the lesional pattern is too acute for the intervention of this cell population. This finding has been described in other diseases caused by intracellular pathogens such as Mycobacterium bovis (Salguero et al 2016). However, the role of these 'nests' in the host immune response is not well understood.…”

Section: Discussionsupporting

confidence: 54%

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Histopathological and immunohistochemical characterization of Burkholderia pseudomallei lesions in an acute model of infection with BALB/c mice

García-Jiménez

Salguero

D’Elia

2017

Int J Experimental Path

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SummaryOrgan tissue damage is a key contributor to host morbidity and mortality following infection with microbial agents. Severe immune responses, excessive cellular recruitment and necrosis of cells all play a role in disease pathology. Understanding the pathogenesis of disease can aid in identifying potential new therapeutic targets or simply act as a diagnostic tool. Burkholderia pseudomallei is a Gram‐negative bacterium that can cause acute and chronic diseases. The BALB/c mouse has been shown to be highly susceptible to aerosol challenge with B. pseudomallei and hence acts as a good model to study the acute and potentially lethal form of the disease melioidosis. In our study, BALB/c mice were challenged and culled at predetermined time points to generate a pathological time course of infection. Lung, liver and spleen were subjected to pathological and immunohistochemical analysis. The number and type of microscopic lesions within each organ, as well as the location and the mean percentage of neutrophils, B cells, T cells and Burkholderia capsule antigen within the lesions, were all characterized during the time course. Neutrophils were determined as the key player in tissue pathology and generation of lesions, with B cells playing an insignificant role. This detailed pathological assessment increases our understanding of B. pseudomallei disease.

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Section: Discussionsupporting

confidence: 54%

“…This finding has been described in other diseases caused by intracellular pathogens such as Mycobacterium bovis (Salguero et al . ). However, the role of these ‘nests’ in the host immune response is not well understood.…”

Section: Discussionmentioning

confidence: 97%

Histopathological and immunohistochemical characterization of Burkholderia pseudomallei lesions in an acute model of infection with BALB/c mice

García-Jiménez

Salguero

D’Elia

2017

Int J Experimental Path

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“…tracheobronchial or mediastinal) [26], other studies have not identified which thoracic lymph nodes were examined or have pooled findings from both tracheobronchial and mediastinal lymph nodes [14, 16, 19, 21]. Disparate cytokine expression patterns between tracheobronchial and caudal mediastinal lymph nodes, as seen in the present study may be partially due to the afferent lymphatics serving these closely associated lymph nodes.…”

Section: Discussionmentioning

confidence: 62%

“…One study found greater TGF-β by IHC in late stage bovine granulomas compared to early stage granulomas [10]. Two separate studies found lower expression of TGF-β mRNA in stage IV granulomas of cattle compared to stage I granulomas [19] with increased expression in stage II granulomas [14]. In macaques, TGF-β may be a chief cytokine in driving tissue repair in active tuberculosis [34].…”

Section: Discussionmentioning

confidence: 99%

Differential Cytokine Gene Expression in Granulomas from Lungs and Lymph Nodes of Cattle Experimentally Infected with Aerosolized Mycobacterium bovis

2016

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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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“…infection. These have also been used in other granulomatous diseases that share some, though not all properties with VL [ 15 – 18 ]. Additionally these techniques can be utilised to evaluate the cellular mechanism of new vaccines, drugs and treatment regimens [ 19 – 21 ].…”

Section: Discussionmentioning

confidence: 99%

Histopathological and immunohistochemical characterisation of hepatic granulomas in Leishmania donovani-infected BALB/c mice: a time-course study

et al. 2018

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BackgroundVisceral leishmaniasis (VL) is a neglected tropical disease (NTD), caused by the intracellular protozoan parasites Leishmania donovani and Leishmania infantum. Symptomatic VL is considered fatal when left untreated. At present, there is no effective vaccine licensed for human use and available chemotherapies have limitations. Understanding the local immune mechanisms required for the control of infection is a key factor for developing effective vaccines and therapeutics.MethodsWe have investigated the development of the typical granulomatous lesions in the liver in experimental VL over time, together with the local immune responses. BALB/c mice were infected intravenously with a dose of 2 × 107 L. donovani amastigotes (MHOM/ET/67/HU3) and sacrificed at 15, 35 and 63 days post-infection (dpi). Histopathology and immunohistochemical techniques were used for the detection of Leishmania antigen, selected cell types including B and T lymphocytes, macrophages and neutrophils (CD45R-B220+, CD3+, F4/80+ and Ly-6G+) and iNOS.ResultsGranulomatous lesions were identified as early as 15 dpi in the livers of all infected animals. Three categories were used to classify liver granulomas (immature, mature and clear). Clear granulomas were exclusively detected from 35 dpi onwards. Kupffer cells (F4/80+) were predominant in immature granulomas, regardless of the dpi. Nonetheless, the highest expression was found 63 dpi. Positive staining for iNOS was mainly observed in the cytoplasm of fused Kupffer cells and the highest expression observed at 35 dpi. T cells (CD3+) and B cells (CD45R-B220+) were predominant in more advanced granuloma stages, probably related to the establishment of acquired immunity. Neutrophils (Ly-6G+) were predominantly observed in mature granulomas with the highest expression at 15 dpi. Neutrophils were lower in numbers compared to other cell types, particularly at later time points.ConclusionsOur results reflect the role of macrophages during the early stage of infection and the establishment of a lymphocytic response to control the infection in more advanced stages.

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Differential Cell Composition and Cytokine Expression Within Lymph Node Granulomas from BCG-Vaccinated and Non-vaccinated Cattle Experimentally Infected with Mycobacterium bovis

Cited by 33 publications

References 42 publications

Histopathological and immunohistochemical characterization of Burkholderia pseudomallei lesions in an acute model of infection with BALB/c mice

Histopathological and immunohistochemical characterization of Burkholderia pseudomallei lesions in an acute model of infection with BALB/c mice

Differential Cytokine Gene Expression in Granulomas from Lungs and Lymph Nodes of Cattle Experimentally Infected with Aerosolized Mycobacterium bovis

Histopathological and immunohistochemical characterisation of hepatic granulomas in Leishmania donovani-infected BALB/c mice: a time-course study

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