Sertoli cells as potential agents against mycobacterial infections

Antibiotic-resistant tuberculosis is a worldwide health threat responsible for hundreds of thousands of deaths each year. The continuous escalation of multidrug resistance demands efforts to identify effective novel therapy approaches against mycobacteria, where selective pressure on the pathogen is not the only treatment goal. In this perspective, Sertoli cells (SCs), originally considered as "sustentacular cells" in the testis, have been elevated to cells of the immune system owing to their capacity to modulate the immune response. As such, they express immunoregulatory factors with a remarkable phagocytic capacity and anti-bacterial activity. The aim of the present study was to explore whether SCs could play a role in the treatment of mycobacteria infections that, to the best of our knowledge, has never been reported before.

Neonatal porcine SCs monolayer were co-cultured with three different concentrations of Mycobacterium bovis Bacillus Calmette and Guerin for 48 h. The phagocytic activity of SCs and the interaction between mycobacteria and SCs have been investigated by the uptake experiment and electron microscopy analysis, respectively. The intra- and extracellular antibacterial activities of SCs have been evaluated by measuring their killing performances.

SCs were shown capable of phagocyting mycobacteria while remaining viable and maintaining ultrastructure integrity. Even at higher mycobacterial concentrations, SCs demonstrated an intracellular killing activity with a Logarithmic reduction of 0.4 Log₁₀ CFU/ml up to 7 days and an extracellular killing activity with a Logarithmic reduction of 1 Log₁₀ CFU/ml up to 10 days post-infection.

This study provided evidence that SCs could be a potentially valuable therapeutic tool for the treatment of mycobacterial infections, such as tuberculosis, by exerting a direct and indirect antibacterial action.