Immunomodulation of ALT-2 and TLR may collude in antigen specific T cell hyporesponsiveness: Proposed mechanism for elevated IL-10 levels in Balb/C mice

Abstract

ALT-2, a novel antigen belonging to the chromadorea ALT-2 family of the filarial nematode is proved to clear filarial parasites in Jirds. In order to increase the protection efficacy by stimulating the cell mediated immunity, MPLA a detoxified derivative of LPS known to induce the cellular response, was used in this study as an adjuvant on mice models. ALT-2+MPLA formulation elicited a high titer of total IgG antibody, with profoundly increased levels of IgG2b. Reduced splenocyte proliferation was observed in immunized group when compared to control groups which could be attributed to many in vivo factors. The levels of IFN-γ were high in unstimulated MPLA group compared to ALT-2 stimulated MPLA group, suggesting that the ALT-2 antigen suppressed the IFN-γ levels. A high level of IL-10 was induced by the ALT-2+MPLA formulation, which inhibited the production of Th2 cytokines (IL-4, IL-5) and also reduced the Th1 cytokine (IFN-γ, IL-2) levels which are not in vogue with the classical MPLA adjuvant formulation. We propose a mechanism for this immunomodulation which involves a diminished expression of TLR-4, by which the filarial parasites have evolved to evade host immune mechanism.

Cloning, expression and characterization of Brugia malayi abundant larval protein transcript-2 (BmALT-2) expressed in Pichia pastoris

“…A chimeric protein construct comprising thioredoxin, transglutaminase and abundant larval transcript-2 (ALT-2) showed enhanced immunological response [48]. The hyper responsiveness of ALT-2 is also well documented with its T-cell and B-cell-specific responses [49,50]. The reactivity of ALT-2 protein with human clinical sera was tested by ELISA using EN, MF and CP sera (n D 10) from endemic regions.…”