**6. Immune profile of active BU patients, exposed and unexposed controls**

Screening for cytokines and antibodies specific responses in BU patients is still a matter of intense research [59, 60, 69–75]. This is because individuals with active disease are incapable of mounting an effective specific immune response to *M. ulcerans* [63]. It is known that patients seem to have reduced expression of Th1 cytokines [49, 69, 70]. In comparison, Th2 response is common among active ulcerative patients and those with healed ulcers [69, 70]. The Th2 cytokine cells include interleukin (IL) 4, IL-5, IL-6, and IL-10. Exposed household contact with no clinical symptoms also have Th2 response [69, 70]. However, BU patients are more likely to express IL-4 and IL-10 [69, 70, 76]. Th1 immune response is characterised by expression of IFNγ and IL-12, critical mediators for macrophages recruitments [66, 69, 70, 76]. Interestingly, previous studies have shown that histopathology of ulcerative tissue biopsy shows macrophages with acid fast bacteria overload (likely to be *M. ulcerans*) [73, 77]. Mycolactone functions to either supress or deviate immune cells that could lead to the effective clearance of *M. ulcerans* from the host [61, 78]. Therefore, first responder cytokines such as tumour necrotic factors (TNF) is downregulated. TNF is responsible for septic shock and it works in concert with IL-17 in the release of inflammation infiltrates to infected areas and induces fever [60, 79].
