In vitro cytokine profiles and viability of different human cells treated with whole cell lysate of Mycobacterium avium subsp. paratuberculosis

Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic inflammation of intestines in cattle and other ruminants, known as Johne’s disease (JD) [1]. MAP infection in JD leads to an early proinflammatory and cytotoxic response (Th-1 like) that further escalates to a predominant antibody based immune response (Th-2 like). Furthermore, studies have demonstrated that MAP infected cattle show enhanced IL-8 gene expression in intestinal tissues when compared to controls [2]. Studies on ovine macrophages indicated that MAP can induce low level apoptosis but not cytotoxicity (necrosis) [3]. MAP, an obligate zoonotic pathogen is also 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]. Moreover, this disease is also considered as an autoimmune disorder with inflammation contributed by Th1 cytokine responses [7]. Studies have also suggested that Crohn’s disease might have a genetic link such as mutation in the NOD2 gene [8]. The epidemiological studies have indicated that Crohn’s disease is more common in the temperate regions of the globe with intensive farming [9]. Diseased animals with clinical JD may shed MAP in their milk and faeces, and it is observed that MAP resists chlorination and pasteurization [10]. The existence of MAP in sphaeroplast form in addition to its bacillary form ensures survival [11]. ELISA studies have indicated correlation between MAP infection and type 1 diabetes mellitus (T1DM) [12,13]. It has been reported that children exposed to MAP in early life have low incidence of certain autoimmune diseases and exposure to MAP is associated with raised antibody levels against MAP [14-16].In both cattle and humans, there is a long delay between the MAP infection and occurrence of the clinical disease. The clinical manifestation could ultimately be the outcome of various cytokine responses of an activated immune system una