Epithelial processed Mycobacterium avium subsp. paratuberculosis induced prolonged Th17 response and suppression of phagocytic maturation in bovine peripheral blood mononuclear cells

Abstract

Johne’s disease (JD) caused by Mycobacterium avium subsp. paratuberculosis (MAP) is a chronic, wasting infectious disease in ruminants that causes enormous economic losses to the dairy and beef cattle industries. Understanding the mechanism of persistency of MAP is key to produce novel ideas for the development of new diagnostic methods or prevention techniques. We sought interactions between the host and MAP using epithelial passage model, which mimic initial stage of infection. From the transcriptomic analysis of bovine immune cells (PBMCs), it was suggested that infection through the epithelial cells elicited prolonged Th17-derived immune response, as indicated by upregulation of IL-17A, IL-17F and RORC until 120 h p.i., compared to directly infected PBMCs. Global downregulation of gene expression was observed after 72 h p.i., especially for genes encoding cell surface receptors of phagocytic cells, such as Toll-like receptors and MHC class II molecules. In addition, the cholesterol efflux transporters ABCA1, ABCG1, and APOE, which are regulated by the LXR/RXR pathway, were downregulated. In summary, it would be suggested that the host initiate immune response to activate Th17-derived cytokines, and MAP survives persistently by altering the host adaptive immune response by suppressing surface receptors and manipulating lipid metabolism in phagocytic cells.

Revealing immune responses in the Mycobacterium avium subsp. paratuberculosis-infected THP-1 cells using single cell RNA-sequencing

“…Moreover, the immune regulatory role of IL-10 has been considered to contribute to the persistence of MAP in the host immune system. Recently, the Th17-like response has been thought to be a major response to MAP infection associated with granuloma formation [33][34][35]. Early expression of Th17-induced cytokines such as IL-17a is associated with activation of innate T lymphocytes induced by IL-1β, IL-6, and IL-23 produced by phagocytic cells [9].…”

Synergistic antibacterial effects of ultrasound combined nanoparticles encapsulated with cellulase and levofloxacin on Bacillus Calmette-Guérin biofilms

“…The cytokines TNF-α, IL-1α and IL-6 promote the synthesis of acute phase proteins such as C-reactive protein, by hepatocytes, the concentration of which is significantly increased during bacterial infection or tissue damage . In contrast, IFN-γ can be used to treat chronic granulomas, malignancies and infectious diseases, among others (Bokhari et al, 2008;Shen et al, 2017;Park et al, 2020). After treatment, cytokines 10.3389/fmicb.2023.1108064 Frontiers in Microbiology frontiersin.org in the murine serum from each group were tested by ELISA test (Figure 10).…”

A framework for non-preserved consensus gene module detection in Johne's disease

“…TREM1 strengthens the inflammatory response to invading microbes and has a key role in protective innate immunity during MAP infection ( 17 , 61 ). This gene has been downregulated in MAP-infected animals, and it seems to be as a result of MAP invasion, which causes the host cell to suppress the expression of surface receptors such as TLRs and MHC class II molecules (required for pathogen recognition) ( 62 ). GCH1 is another hub gene of the sienna3 module with a significant SNP associated with MAP infection ( 22 ).…”