Abstract
Mycobacterium avium subsp. paratuberculosis (MAP) is a zoonotic pathogen, a very slow growing bacterium which is difficult to isolate and passage in conventional laboratory culture. Although its association with Johne’s disease or paratuberculosis of cattle is well established, it has been only putatively linked to Crohn’s disease in humans. Further, MAP has been recently suggested to be a trigger for other autoimmune diseases such as type-1 diabetes mellitus (T1DM). Recently, some studies have indicated that exposure to MAP is associated with elevated levels of antibodies against MAP lysate although the exact mechanism and significance of the same remains unclear. Further, the cytokine profiles relevant in MAP associated diseases of humans and their exact role in the pathophysiology are not clearly known. We performed in vitro cytokine analyses after exposing different cultured human cells to the whole cell lysate of MAP and found that MAP lysate induces secretion of cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α by human peripheral blood mononuclear cells (PBMCs). Also, it induces secretion of IL-8 by cultured human stomach adenocarcinoma cells (AGS) and PANC-1(human pancreatic carcinoma cell line) cells. We also found that MAP lysate induced cytotoxicity in PANC-1cells. Collectively, these results provide a much needed base-line data set of cytokines broadly signifying a MAP induced cellular response by human cells.
Highlights
Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic inflammation of intestines in cattle and other ruminants, known as Johne’s disease (JD) [1]
These included the treatment of human peripheral blood mononuclear cells (PBMCs) with MAP lysate that resulted in an increased secretion of cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α in a dose and time dependent manner (Figure 1A)
The cytokine responses from the human PBMCs were from two normal humans who presumably have not been exposed to MAP
Summary
Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic inflammation of intestines in cattle and other ruminants, known as Johne’s disease (JD) [1]. Paratuberculosis (MAP) causes chronic inflammation of intestines in cattle and other ruminants, known as Johne’s disease (JD) [1]. Studies have demonstrated that MAP infected cattle show enhanced IL-8 gene expression in intestinal tissues when compared to controls [2]. MAP, an obligate zoonotic pathogen is linked to a similar type of enteritis as JD, in humans, known as Crohn’s disease [4,5], wherein, the symptoms include abdominal pain, ulcers and diarrhoea (with bloody episodes) [6].
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