Onchocerciasis modulates the immune response to mycobacterial antigens

Chronic helminth infection induces a type-2 cellular immune response. Tn co ntrast to this, mycobacterial infections commonly induce a type-1 immune re sponse which is considered protective. Type-2 responses and diminished type -1 responses to mycobacteria have been previously correlated with active in fection states such as pulmonary tuberculosis and lepromatous leprosy. The present study examines the immune responses of children exposed to both the helminth parasite Onchocerca volvulus and the mycobacterial infections, My cobacterium tuberculosis and M. leprae. Proliferation of peripheral blood m ononuclear cells (PBMC) and production of IL-4 in response to both helminth and mycobacterial antigen (PPD) decreased dramatically with increasing mic rofilarial (MF) density. Although interferon-gamma (IFN-gamma) production s trongly correlated with cellular proliferation, it was surprisingly not rel ated to MF density for either antigen. IL-4 production in response to helmi nth antigen and PPD increased with ascending children's age. IFN-gamma and cellular proliferation to PPD were not related to age, but in response to h elminth antigen were significantly higher in children of age 9-12 years tha n children of either the younger age group (5-8 years) or the older group ( 13-16 years). Thus, there was a MF density-related down-regulation of cellu lar responsiveness and age-related skewing toward type 2 which was parallel ed in response to both the helminth antigen and PPD. This parasite-induced immunomodulation of the response to mycobacteria correlates with a previous report of doubled incidence of lepromatous leprosy in onchocerciasis hyper endemic regions. Moreover, this demonstration that helminth infection in hu mans can modulate the immune response to a concurrent infection or immunolo gical challenge is of critical importance to future vaccination strategies.