02969nas a2200409 4500000000100000008004100001260001300042653001500055653001200070653002300082653002000105653001000125653002100135653001100156653002100167653001800188653001200206653002800218653002500246653003100271653002400302653003900326653001500365653001700380100001600397700001700413700001400430700001200444700001300456700001600469245007600485856007800561300001100639490000800650520188700658022001402545 1999 d c1999 Sep10aAdolescent10aAnimals10aAntigens, Helminth10aCells, Cultured10aChild10aChild, Preschool10aHumans10aInterferon-gamma10aInterleukin-410aleprosy10aLeukocytes, Mononuclear10aMycobacterium leprae10aMycobacterium tuberculosis10aOnchocerca volvulus10aonchocerciasis elimination mapping10aTuberculin10aTuberculosis1 aStewart G R1 aBoussinesq M1 aCoulson T1 aElson L1 aNutman T1 aBradley J E00aOnchocerciasis modulates the immune response to mycobacterial antigens. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905356/pdf/cei0117-0517.pdf a517-230 v1173 a

Chronic helminth infection induces a type-2 cellular immune response. In contrast to this, mycobacterial infections commonly induce a type-1 immune response which is considered protective. Type-2 responses and diminished type-1 responses to mycobacteria have been previously correlated with active infection 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, Mycobacterium tuberculosis and M. leprae. Proliferation of peripheral blood mononuclear cells (PBMC) and production of IL-4 in response to both helminth and mycobacterial antigen (PPD) decreased dramatically with increasing microfilarial (MF) density. Although interferon-gamma (IFN-gamma) production strongly correlated with cellular proliferation, it was surprisingly not related to MF density for either antigen. IL-4 production in response to helminth 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 helminth antigen were significantly higher in children of age 9-12 years than 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 cellular responsiveness and age-related skewing toward type 2 which was paralleled 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 hyperendemic regions. Moreover, this demonstration that helminth infection in humans can modulate the immune response to a concurrent infection or immunological challenge is of critical importance to future vaccination strategies.

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