MR1-restricted mucosal-associated invariant T (MAIT) cells respond to mycobacterial vaccination and infection in nonhuman primates.

Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts. Using the macaque MR1 tetramer we show that NHP MAITs activated in vivo in response to both Bacillus Calmette-Guerin vaccination and Mycobacterium tuberculosis infection. These results demonstrate that NHP and human MR1 and MAITs function analogously, and establish a preclinical animal model to test MAIT-targeted vaccines and therapeutics for human infectious and autoimmune disease.

Experimental exposure of zebrafish, Danio rerio (Hamilton), to Mycobacterium marinum and Mycobacterium peregrinum reveals the gastrointestinal tract as the primary route of infection: a potential model for environmental mycobacterial infection.

The natural route by which fish become infected with mycobacteria is unknown. Danio rerio (Hamilton) were exposed by bath immersion and intubation to Mycobacterium marinum and Mycobacterium peregrinum isolates obtained from diseased zebrafish. Exposed fish were collected over the course of 8 weeks and examined for the presence of mycobacteriosis. Mycobacteria were consistently cultured from the intestines, and often from the livers and spleens of fish exposed by both methods. Mycobacteria were not observed in the gills. Histological analysis revealed that fish infected with M. marinum often developed granulomas accompanied by clinical signs of mycobacteriosis, while infection with M. peregrinum infrequently led to clinical signs of disease. Passage of the bacteria through environmental amoebae (Acanthamoeba castellani) was associated with increased growth of M. peregrinum over the course of 8 weeks, when compared to infection with the bacteria not passed through amoebae. The results provide evidence that zebrafish acquire mycobacteria primarily through the intestinal tract, resulting in mycobacterial dissemination.