Onchocerciasis modulates the immune response to mycobacterial antigens

Abstract

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.

Fig. 1

Proliferation of peripheral blood mononuclear cells (PBMC) from children resident in a region hyperendemic for onchocerciasis. PBMC were stimulated with: (a) adult female Onchocerca volvulus antigen (OvAg); (b) Mycobacterium tuberculosis PPD; (c) phytohaemagglutinin (PHA). (a) OvAg-stimulated cells were significantly influenced by age category and microfilariae (MF) (χ² = 4.6, d.f. = 2 and χ² = 4.5, d.f. = 2, respectively; P < 0.05 in both cases). (b) PPD-stimulated cells were significantly influenced by MF (χ² = 4.18, d.f. = 1.48; P < 0.05). (c) PHA-stimulated cells were influenced by age as a linear variate (χ² = 4.96, d.f. = 1; P < 0.05). Mean ct/min in medium alone = 652, s.e.m. = 98.

Fig. 2

IL-4 production by peripheral blood mononuclear cells (PBMC) stimulated with: (a) adult female Onchocerca volvulus antigen (OvAg); (b) mycobacterial antigen (PPD). (a) Age as a categorical variable and intensity of microfilariae (MF) significantly influenced OvAg-stimulated IL-4 production (χ² = 5.1, d.f. = 2 and χ² = 7.3, d.f. = 2, respectively; P < 0.05 in both cases). (b) Both age as a linear variate and intensity of MF influenced PPD-stimulated IL-4 production (χ² = 7.2, d.f. = 2 and χ² = 5.3, d.f. = 2, respectively; P < 0.05 in both cases).

Fig. 3

IFN-γ production by peripheral blood mononuclear cells (PBMC) stimulated with: (a) adult female Onchocerca volvulus antigen (OvAg); (b) mycobacterial antigen (PPD). (a) Age was significantly influential to OvAg-stimulated IFN-γ production both as a quadratic variate (χ² = 6.7, d.f. = 2, P < 0.05) and a categorical variable (χ² = 6.4, d.f. = 2, P < 0.05). (b) PPD-stimulated IFN-γ production was significantly influenced by bacille Calmette–Guérin (BCG) vaccination status, b (χ² = 4.2, d.f. = 1, P < 0.05), and also by sex with males producing higher levels of IFN-γ (χ² = 7.3, d.f. = 1, P < 0.05). Error bars = s.e.m.