Abstract
BackgroundDifferences in immune responses against different lineages of Mycobacterium tuberculosis (Mtb), and by different types of immune cell, are still poorly understood. We aimed to compare the secretome-based immune responses among three Mtb lineages and among immune-cell types. The immune responses were also investigated during infection and when the bacilli had been eliminated from the immune cells.MethodsHuman primary leukocytes were infected with strains representing three lineages of Mtb (East-Asian, Indo-Oceanic and Euro-American). Label-free GeLC MS/MS proteomic analysis of secretomes was performed. The response of each immune-cell type was compared with the appropriate interactome database for each.ResultsThe expression pattern of proteins secreted by Mtb-infected leukocytes differed among Mtb lineages. The ancestral lineage (IO lineage) had a greater ability to activate MMP14 (associated with leukocyte migration) than did the more recent lineages (EA and EuA). During infection, proteins secreted by macrophages, dendritic cells, neutrophils and B-cells were associated with cell proliferation. Following clearance of Mtb, proteins associated with interferon signaling were found in macrophages, dendritic cells and neutrophils: proteins associated with antigen processing were found in B-cells and regulatory T-cells. Expression of immune response-related proteins from many immune-cell types might be suppressed by Mtb infection. Our study has provided a better insight into the host-pathogen interaction and immune response against different Mtb lineages.
Highlights
Tuberculosis (TB) is the most important infectious disease globally, causing 10 million new cases and causing 1.5 million deaths annually (WHO, 2019)
The CFU plate count showed that Mycobacterium tuberculosis (Mtb) cells were present in the leukocytes during the infection stage of the experiment but that no Mtb cells remained at the clearance stage (Day 5) (Table S4)
We demonstrated that the proteins secreted by Mtb-infected leukocytes differed according to the Mtb lineage involved
Summary
Tuberculosis (TB) is the most important infectious disease globally, causing 10 million new cases and causing 1.5 million deaths annually (WHO, 2019). Characterisation of secretome-based immune responses of human leukocytes infected with various Mycobacterium tuberculosis lineages. It remains uncertain whether the immune response varies according to the lineage of Mtb involved, or according to the type of immune cell involved in the host response. Differences in immune responses against different lineages of Mycobacterium tuberculosis (Mtb), and by different types of immune cell, are still poorly understood. We aimed to compare the secretome-based immune responses among three Mtb lineages and among immune-cell types. The expression pattern of proteins secreted by Mtb-infected leukocytes differed among Mtb lineages. Proteins secreted by macrophages, dendritic cells, neutrophils and B-cells were associated with cell proliferation. Expression of immune response-related proteins from many immune-cell types might be suppressed by Mtb infection. Our study has provided a better insight into the host-pathogen interaction and immune response against different Mtb lineages
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