Modulation of immune response to 35 kda protein of Mycobacterium avium paratuberculosis using Ribi adjuvant

AbstractJohne’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.

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Notch-1 Signaling Modulates Macrophage Polarization and Immune Defense against Mycobacterium avium paratuberculosis Infection in Inflammatory Diseases

Microorganisms ◽

10.3390/microorganisms8071006 ◽

2020 ◽

Vol 8 (7) ◽

pp. 1006 ◽

Cited By ~ 1

Author(s):

Esra’a Keewan ◽

Saleh A. Naser

Keyword(s):

Inflammatory Response ◽

Notch Signaling ◽

Mycobacterium Avium ◽

Macrophage Polarization ◽

Immune Defense ◽

Notch 1 ◽

Macrophage Response ◽

Mycobacterium Avium Paratuberculosis ◽

Vitro Effect

Despite the extensive research on Notch signaling involvement in inflammation, its specific role in macrophage response in autoimmune disease and defense mechanisms against bacterial infection, such as Mycobacterium avium paratuberculosis (MAP), remains unknown. In this study, we investigated the molecular role of Notch-1 signaling in the macrophage response during MAP infection. In particular, we measured the in vitro effect of MAP on Notch-1 signaling and downstream influence on interleukin (IL)-6 and myeloid cell leukemia sequence-1 (MCL-1) and consequent cellular apoptosis, MAP viability, and macrophage polarization. Overall, the data show significant upregulation in Notch-1, IL-6, and MCL-1 in MAP-infected macrophages, parallel with a decrease in apoptosis and elevated pro-inflammatory response in these infected cells. On the contrary, blocking Notch signaling with γ-secretase inhibitor (DAPT) decreased MAP survival and burden, increased apoptosis, and diminished the pro-inflammatory response. In particular, the treatment of infected macrophages with DAPT shifted macrophage polarization toward M2 anti-inflammatory phenotypic response. The outcome of this study clearly demonstrates the critical role of Notch signaling in macrophage response during infection. We conclude that MAP infection in macrophages activates Notch-1 signaling and downstream influence on IL-6 which hijack MCL-1 dependent inhibition of apoptosis leading to its chronic persistence, and further inflammation. This study supports Notch-1 signaling as a therapeutic target to combat infection in autoimmune diseases such as Crohn’s disease and Rheumatoid Arthritis.

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Antibodies Induced by Lipoarabinomannan in Bovines: Characterization and Effects on the Interaction betweenMycobacterium aviumSubsp.paratuberculosisand MacrophagesIn Vitro

Veterinary Medicine International ◽

10.4061/2011/258479 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Ana Jolly ◽

Silvia Beatriz Colavecchia ◽

Bárbara Fernández ◽

Eloy Fernández ◽

Silvia Leonor Mundo

Keyword(s):

Immune Response ◽

Mycobacterium Avium ◽

Active Role ◽

Macrophage Cell Line ◽

Macrophage Cell ◽

Specific Antibodies ◽

Humoral Immune ◽

Bovine Macrophage

Lipoarabinomannan (LAM) is a major glycolipidic antigen on the mycobacterial envelope. The aim of this study was to characterize the humoral immune response induced by immunization with a LAM extract in bovines and to evaluate the role of the generated antibodies in thein vitroinfection of macrophages withMycobacterium aviumsubsp.paratuberculosis(MAP). Sera from fourteen calves immunized with LAM extract or PBS emulsified in Freund's Incomplete Adjuvant and from five paratuberculosis-infected bovines were studied. LAM-immunized calves developed specific antibodies with IgG1 as the predominant isotype. Serum immunoglobulins were isolated and their effect was examined in MAP ingestion and viability assays using a bovine macrophage cell line. Our results show that the antibodies generated by LAM immunization significantly increase MAP ingestion and reduce its intracellular viability, suggesting an active role in this model.

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