People in regions of Schistosoma mansoni endemicity slowly acquire immunity, but why this takes years to develop is still not clear. It has been associated with increases in parasite-specific
IgE, induced, some investigators propose, to
antigens exposed during the death of adult worms. These
antigens include members of the tegumental-
allergen-like
protein family (TAL1 to TAL13). Previously, in a group of S. mansoni-infected Ugandan males, we showed that
IgE responses to three TALs expressed in worms (TAL1, -3, and -5) became more prevalent with age. Now, in a subcohort we examined associations of these responses with resistance to
reinfection and use the data to propose a mechanism for the slow development of immunity.
IgE was measured 9 weeks posttreatment and at
reinfection at 2 years (n = 144). An anti-TAL5
IgE (herein referred to as TAL5
IgE) response was associated with reduced
reinfection even after adjusting for age using regression analysis (geometric mean odds ratio, 0.24; P = 0.016). TAL5
IgE responders were a subset of TAL3
IgE responders, themselves a subset of TAL1 responders. TAL3
IgE and TAL5
IgE were highly cross-reactive, with TAL3 the immunizing
antigen and TAL5 the cross-reactive
antigen. Transcriptional and translational studies show that TAL3 is most abundant in adult worms and that TAL5 is most abundant in infectious larvae. We propose that in chronic
schistosomiasis, older individuals have repeatedly experienced
IgE antigens exposed when adult worms die (e.g., TAL3) and that this leads to increasing cross-reactivity with
antigens of invading larvae (e.g., TAL5). Progressive accumulation of worm/larvae cross-reactivity could explain the age-dependent immunity observed in areas of endemicity.