A Xenopus tadpole alternative model to study innate-like T cell-mediated anti-mycobacterial immunity

Owing to the high incidence of multi-drug resistance and challenges posed by the complex and long duration of treatments, Mycobacterium tuberculosis (Mtb) infections remain a significant clinical burden, which would benefit from development of novel immuno-therapeutic-based treatment strategies. Among early immune effectors, invariant or innate-like (i)T cells are attracting attention because of their potential regulatory activity, which can shape anti-mycobacterial immune responses. Unlike conventional T cells, iT cells express a semi-invariant T cell receptor, and respond rapidly and robustly to molecular patterns presented by MHC class I-like molecules. To date, functional studies of iT cells in vivo has been problematic and the role of iT cells in anti-Mtb responses remains unclear. Here, after reviewing the recent literature on anti-mycobacterial iT cell immunity, we describe a novel alternative model system in the amphibian Xenopus laevis tadpoles during infection with Mycobacterium marinum (Mm). X. laevis tadpoles rely mostly on a few distinct prominent innate-like (i)T cell subsets, whose development and function are governed by distinct MHC class I-like molecules. Thus, X. laevis tadpoles provide a convenient and cost-effective in vivo model uniquely suited to investigate the roles of iT cells during mycobacterial infections. We have developed reverse genetics and MHC tetramer technology to characterize this MHC-like/iT system in tadpoles. Our study in X. laevis provides evidence of a conserved convergent function of iT cells in host defenses against mycobacteria between mammals and amphibians.