Comparison of human monocyte derived macrophages and THP1-like macrophages as in vitro models for M. tuberculosis...

Macrophages are the preferential cell types to study various aspects of mycobacterial infection. Commonly used infection models for in-vitro studies are primary macrophages such as human monocyte derived macrophages (hMDMs) and macrophage like cell lines (THP-1). It is not clear if commercially available THP-1 cells can be used as hMDMs alternative for in-vitro M.tb infection experiments. We conducted a detailed investigation of the hMDM and THP-1 response to mycobacterial infection on a comparative basis and assess the most crucial aspects of infection which are most commonly studied. We assessed mycobacterial uptake and intracellular growth over time of a pathogenic drug-resistant and drug-susceptible M.tb strains (R179 and H37Rv) through colony forming units (CFUs). Both strains depicted similar uptake and intracellular growth in hMDMs and THP-1 macrophages over time (R179, p = 0.954) (H37Rv, p = 0.922). Cytotoxicity assays revealed a consistent viability up to day 16 post-infection across the strains in both THP-1 and hMDMs (R179, p = 0.271) (H37Rv, p = 0.068). Interestingly, both cell lines showed similar mycobacterial uptake and cellular viability in both susceptible as well as resistant M.tb strains. Cytokine/chemokine mRNA analysis through qPCR found no difference between cell types. Further, cytokine secretion measured through Luminex revealed no difference across the strains. Also, cytokine secretion analysis showed no difference in both cell lines across strains. In conclusion, our study shows that THP-1 and hMDMs bacterial uptake, viability and host response to drug-susceptible and drug-resistant mycobacterial infections are similar. Therefore, present study demonstrate that THP-1 cells are suitable substitutes for hMDMs for in-vitro M.tb infection experiments.