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Measuring bovine ?? T cell function at the site of Mycobacterium bovis infection.

ABSTRACT: Bovine ?? T cells are amongst the first cells to accumulate at the site of Mycobacterium bovis infection; however, their role in the developing lesion remains unclear. We utilized transcriptomics analysis, in situ hybridization, and a macrophage/?? T cell co-culture system to elucidate the role of ?? T cells in local immunity to M. bovis infection. Transcriptomics analysis revealed that ?? T cells upregulated expression of several novel, immune-associated genes in response to stimulation with M. bovis antigen. BCG-infected macrophage/?? T cell co-cultures confirmed the results of our RNAseq analysis, and revealed that ?? T cells from M. bovis-infected animals had a significant impact on bacterial viability. Analysis of ?? T cells within late-stage M. bovis granulomas revealed significant expression of IFN-? and CCL2, but not IL-10, IL-22, or IL-17. Our results suggest ?? T cells influence local immunity to M. bovis through cytokine secretion and direct effects on bacterial burden.

SUBMITTER: Rusk RA

PROVIDER: S-EPMC5703227 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Measuring bovine γδ T cell function at the site of Mycobacterium bovis infection.

Rusk Rachel A RA Palmer Mitchell V MV Waters W Ray WR McGill Jodi L JL

Veterinary immunology and immunopathology 20171027

Bovine γδ T cells are amongst the first cells to accumulate at the site of Mycobacterium bovis infection; however, their role in the developing lesion remains unclear. We utilized transcriptomics analysis, in situ hybridization, and a macrophage/γδ T cell co-culture system to elucidate the role of γδ T cells in local immunity to M. bovis infection. Transcriptomics analysis revealed that γδ T cells upregulated expression of several novel, immune-associated genes in response to stimulation with M. ...[more]

PMID: 29129226

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Project description:Accumulating evidence indicates that antibodies can protect against some intracellular pathogens. Mycobacterium bovis is an intracellular bacterium, and its cell wall (CW) is essential for its virulence and survival. However, the questions of whether antibodies play a protective role in immunity against M. bovis infection and what effects antibodies specific to the CW of M. bovis have still remain unclear. Here, we report that antibodies targeting the CW of an isolated pathogenic M. bovis strain and that of an attenuated bacillus Calmette-Guérin (BCG) strain could induce protection against virulent M. bovis infection in vitro and in vivo. Further research found that the antibody-induced protection was mainly achieved by promoting Fc gamma receptor (FcγR)-mediated phagocytosis, inhibiting bacterial intracellular growth, and enhancing the fusion of phagosomes and lysosomes, and it also depended on T cells for its efficacy. Additionally, we analyzed and characterized the B-cell receptor (BCR) repertoires of CW-immunized mice via next-generation sequencing. CW immunization stimulated BCR changes in the complementarity determining region 3 (CDR3) isotype distribution, gene usage, and somatic hypermutation. Overall, our study validates the idea that antibodies targeting the CW induce protection against virulent M. bovis infection. This study highlights the importance of antibodies targeting the CW in the defense against tuberculosis. IMPORTANCE M. bovis is the causative agent of animal tuberculosis (TB) and human TB. Research on M. bovis is of great public health significance. Currently, TB vaccines are mainly aimed at eliciting protection by enhancement of cell-mediated immunity, and there are few studies on protective antibodies. This is the first report of protective antibodies against M. bovis infection, and the antibodies had both preventive and even therapeutic effects in an M. bovis infection mouse model. Additionally, we reveal the relationship between CDR3 gene diversity and the immune characteristics of the antibodies. These results will provide valuable advice for the rational development of TB vaccines.

Dataset Information

Measuring bovine ?? T cell function at the site of Mycobacterium bovis infection.

Publications

Measuring bovine γδ T cell function at the site of Mycobacterium bovis infection.

Similar Datasets

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