The role and function of lipid-reactive guinea pig T cells in mycobacterial granuloma formation and maintenance

The guinea pig is a naturally susceptible host for virulent mycobacteria. After infection granulomas indistinguishable from those in human tuberculosis patients develop. Like humans, guinea pigs express a functional CD1 system and therefore are an ideal animal model to study the lipid-specific immune responses in the host-pathogen interplay. Guinea pigs were either immunized with the vaccine strain Bacille-Calmette-Guérin (BCG) or liposomes containing the lipid mycobacterial antigen Phosphatidyl-Inositol-hexa-Mannoside (PIM6). After twelve weeks they were challenged with Mycobacterium tuberculosis (Mtb). 4 weeks after infection, blood was obtained, the animals were euthanized and dissected. The groups were compared with respect to antigen-specific T-cell-proliferation, pathology and histopathology. Using RT-qPCR expression of cytokines and CD1-molecules was assessed. Vaccinated animals mount a robust CD1b-restricted T-cell response to PIM, and this is accompanied by an elevated CD1b expression in vaccinated animals as shown by RT-qPCR and In-situ-hybridisation. After infection differences are observed in the upregulation of inflammatory cytokines and chemokines between the groups. Infection with Mtb results in local granuloma formation. Despite the absence of clinical symptoms, infected guinea pigs develop systemic infection with granulomas in lung, spleen and liver. Vaccinated animals show reduced granuloma formation and are protected from mycobacterial dissemination.