Cytokine Responses to Stimulation of Whole Blood from Patients with Buruli Ulcer Disease in Ghana

Abstract

Buruli ulcer disease (BUD), caused byIL-10 and IL-4 levels did not differ between BUD patients and controls, although active TB patients had significantly higher IL-10 production levels than did treated TB patients. Multivariate analysis showed no confounding factors. In conclusion, Th-1 down regulation in early BUD appears to reverse in later stages of BUD, although an association with IL-10 or IL-4 production does not emerge from our data. Here we show differences in Th-1-type cytokine production between early-and late-stage BUD that might reflect an improved immune defense over time.

IFN-γ–Dependent Activation of Macrophages during Experimental Infections by Mycobacterium ulcerans Is Impaired by the Toxin Mycolactone

“…However, we have recently described an intramacrophage growth phase for M. ulcerans (14), showing that although apparently contradictory, the production of a cytotoxic exotoxin can be conciliated with an intracellular lifestyle. These observations are in accordance with the cellular-mediated immune and delayedtype hypersensitivity responses induced in BU patients postinfection and required for M. ulcerans control (9,24,26,39,46,(48)(49)(50)(51). The host immune response is therefore determined by the Furthering the understanding on the immune response against M. ulcerans, we show in this study for the first time that the IFN-gdependent activation of macrophages is required for the host control of this Mycobacterium, as shown by in vitro and in vivo models of infection.…”

“…This cytokine was firstly suggested to play a role in the control of M. ulcerans infections by Gooding et al (24,39), who report that PBMCs from patients with past BU, but not from healthy contacts, display low capacity to produce IFN-g after stimulation with live M. ulcerans or Mycobacterium bovis bacillus Calmette-Guérin (BCG). In a posterior study, Westenbrink et al (51) reported that purified protein derivative-stimulated PBMCs from BU patients produce significantly higher levels of IFN-g in late stages of the disease but not in early stages, as compared with matched community controls. These data were recently confirmed (52).…”

Mycolactone Suppresses T Cell Responsiveness by Altering Both Early Signaling and Posttranslational Events

“…We have recently confirmed this finding on primary T cells using human peripheral blood CD4 + T lymphocytes and have shown that the effects of mycolactone are not restricted to IL-2, since it blocked the activation-induced production of IFN-g, IL-4, IL-17, IL-10, TNF, IL-8, and MIP-1b (15). Several independent studies have reported defective systemic production of IFN-g in patients with active ulcers (16)(17)(18)(19)(20). Our recent multiplex analysis of the immunological profile of BUD patients showed that the production of several other Th1, Th2, and Th17 cytokines was altered.…”

Infection withMycobacterium ulceransInduces Persistent Inflammatory Responses in Mice

“…Indeed, there are several lines of evidence implicating CMI and delayed-type hypersensitivity responses in human M. ulcerans infections, favoring the possible existence of a phase of intracellularity of the pathogen, as follows. Studies with humans show that resistance to M. ulcerans is associated with the Th1 (24,25,26,55,76), while a shift to a Th2 phenotype is related to susceptibility (26), and point to a protective effect of BCG vaccination (46,53,54,63,66,73). Additionally, as BU disease progresses to healing, granuloma formation occurs (30,31,35,40,49,66,74), and the burulin skin test (65) tends to change from negative to positive (13,42).…”