Clinical Disease Upregulates Expression of CD40 and CD40 Ligand on Peripheral Blood Mononuclear Cells from Cattle Naturally Infected with Mycobacterium avium subsp. paratuberculosis

Khalifeh, Mohammad; Stabel, Judith R.

doi:10.1128/cvi.00246-13

Cited by 11 publications

(6 citation statements)

References 34 publications

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“…CD40 and CD86 are costimulatory proteins present on APCs and play a key role in activating T-cell mediated immune responses by presenting processed antigens to CD4 + T cells. Previous studies have demonstrated the role of CD40 and CD86 co-stimulatory proteins in immune cells in MAP infection 34,35 .…”

Section: Discussionmentioning

confidence: 98%

Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice

Gupta

Parlane

Luo

et al. 2020

Sci Rep

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Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic progressive granulomatous enteritis leading to diarrhoea, weight loss, and eventual death in ruminants. Commercially available vaccines provide only partial protection against MAP infection and can compromise the use of bovine tuberculosis diagnostic tests. Here, we report the development of a protein-particle-based vaccine containing MAP antigens Ag85A202–347-SOD1–72-Ag85B173–330-74F1–148+669–786 as a fusion (‘MAP fusion protein particle’). The fusion antigen displayed on protein particles was identified using mass spectrometry. Surface exposure and accessibility of the fusion antigen was confirmed by flow cytometry and ELISA. The MAP fusion protein particle vaccine induced strong antigen-specific T-cell immune responses in mice, as indicated by increased cytokine (IFN-γ and IL-17A) and costimulatory signals (CD40 and CD86) in these animals. Following MAP-challenge, a significant reduction in bacterial burden was observed in multiple organs of the mice vaccinated with the MAP fusion protein particle vaccine compared with the PBS group. The reduction in severity of MAP infection conferred by the MAP fusion protein particle vaccine was similar to that of Silirum and recombinant protein vaccines. Overall, the results provide evidence that MAP antigens can be engineered as a protein particulate vaccine capable of inducing immunity against MAP infection. This utility offers an attractive platform for production of low-cost particulate vaccines against other intracellular pathogens.

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Section: Discussionmentioning

confidence: 98%

Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice

Gupta

Parlane

Luo

et al. 2020

Sci Rep

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show abstract

“…BAFF also plays a pivotal role in promoting the survival of plasmablasts, especially after CD40/CD40LG activation [39]. Proliferation and class switch triggered by CD40/CD40LG and then the prevention of apoptosis by BAFF and AP-1 would push the host’s immune response to one that is Th2 dominated [44]. The reduced expression of this gene in the vaccinated uninfected animals suggests that, at this timepoint, the humoral response in these animals is being down regulated or suppressed.…”

Section: Discussionmentioning

confidence: 99%

The humoral immune response is essential for successful vaccine protection against paratuberculosis in sheep

et al. 2019

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Background The role played by the humoral immune response in animals vaccinated against a mycobacterial disease such as paratuberculosis, is not well understood. Sheep vaccinated against Mycobacterium avium subsp. paratuberculosis (MAP) can still become infected and in some cases succumb to clinical disease. The strength and location of the humoral immune response following vaccination could contribute to the ability of sheep to clear MAP infection. We examined the peripheral antibody response along with the localised humoral response at the site of paratuberculosis infection, the ileum, to better understand how this contributes to MAP infection of sheep following vaccination and exposure. Results Through assessing MAP specific serum IgG1 and IgG levels we show that the timing and strength of the humoral immune response directly relates to prevention of infection following vaccination. Vaccinated sheep that subsequently became infected had significantly reduced levels of MAP specific serum IgG1 early after vaccination. In contrast, vaccinated sheep that did not subsequently become infected had significantly elevated MAP specific serum IgG1 following vaccination. Furthermore, at 12 months post MAP exposure, vaccinated and subsequently uninfected sheep had downregulated expression of genes related to the humoral response in contrast to vaccinated infected sheep where expression levels were upregulated. Conclusions The timing and strength of the humoral immune response following vaccination against paratuberculosis in sheep directly relates to subsequent infection status. An initial strong IgG1 response following vaccination was crucial to prevent infection. Additionally, vaccinated uninfected sheep were able to modulate that response following apparent MAP clearance, unlike vaccinated infected animals where there was apparent dysregulation of the humoral response, which is associated with progression to clinical disease.

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“…Reduced expression of CD40L in the ICV of clinical cows is interesting as the binding of CD40 on APCs with CD40L on activated T-cells initiates a proinflammatory response. Previously, expression of CD40 and CD40L on PBMCs was increased in cows naturally infected with MAP, regardless of stage of infection, upon stimulation of cells with live MAP [ 39 ]. Since CD40L is expressed primarily on activated CD4+ T cells, it is likely that this represents a decreased presence of this cell type within the ICV as reduced numbers of CD4+ T cells have been observed in cattle with clinical disease [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of Ileocecal Valve of Holstein Dairy Cows Infected with Mycobacterium avium subsp. Paratuberculosis

2016

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Johne’s disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advanced clinical stage of infection, are poorly understood. This study examines gene expression in the ileocecal valve (ICV) of Holstein dairy cows at different stages of MAP infection. The ICV is known to be a primary site of MAP colonization and provides an ideal location to identify genes that are relevant to the progression of this disease. RNA was prepared from ICV tissues and RNA-Seq was used to compare gene transcription between clinical, subclinical, and uninfected control animals. Interpretation of the gene expression data was performed using pathway analysis and gene ontology categories containing multiple differentially expressed genes. Results demonstrated that many of the pathways that had strong differential gene expression between uninfected control and clinical cows were related to the immune system, such as the T- and B-cell receptor signaling, apoptosis, NOD-like receptor signaling, and leukocyte transendothelial migration pathways. In contrast, the comparison of gene transcription between control and subclinical cows identified pathways that were primarily involved in metabolism. The results from the comparison between clinical and subclinical animals indicate recruitment of neutrophils, up regulation of lysosomal peptidases, increase in immune cell transendothelial migration, and modifications of the extracelluar matrix. This study provides important insight into how cattle respond to a natural MAP infection at the gene transcription level within a key target tissue for infection.

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Clinical Disease Upregulates Expression of CD40 and CD40 Ligand on Peripheral Blood Mononuclear Cells from Cattle Naturally Infected with Mycobacterium avium subsp. paratuberculosis

Cited by 11 publications

References 34 publications

Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice

Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice

The humoral immune response is essential for successful vaccine protection against paratuberculosis in sheep

Transcriptional Profiling of Ileocecal Valve of Holstein Dairy Cows Infected with Mycobacterium avium subsp. Paratuberculosis

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