Immunopathogenesis of Whipples disease
Most individuals who have been exposed to T. whipplei have resulted in either asymptomatic carriage or a self-limited infection and resulting immunity. Due to the low number of individuals who actually develop Whipple’s disease versus those who have been exposed, it is postulated that a combination of host, bacterial, and environmental factors interplay to allow the disease. Chronic infection with T. whipplei and Whipple’s disease have both been linked to HLA-DRB1∗13 and DQB1∗06 alleles . Certain cytokine profiles have also been linked to Whipple’s disease; whether this is a result of the host, infection, or some combination thereof, is yet to be determined. The overall cytokine profile is that of increased expression of interleukin (IL)-4, IL-10, and CC chemokine ligand 18, and low interferon-γ and low dendritic cell expression of IL-12. Related to these cytokine profiles are diminished functionality of Th1 cells, macrophages, and monocytes and an increased Th2 response. The resulting situation is not only a decreased immune response to T. whipplei and inability to clear the infection but also a manipulation of the immune system, where the bacterium hijacks macrophages and immature dendritic cells and uses these cells for multiplication and spread throughout the body. It has been proposed that IL-16-mediated interference with the endocytic pathway likely contributes to the spread of T. whipplei by inducing bacterial replication and inhibiting phagolysosome formation.
This “chink in the immunological armor” seems to be utilized by T. whipplei only rather than resulting in a widespread immunodeficiency. Individuals with Whipple’s disease do not have associated opportunistic infections. However, in those individuals who have suffered from Whipple’s disease, there is a susceptibility to relapses and reinfections with new strains.
