The nature of the stimulant differentially impacts the innate memory response of monocytes to <i>Mycobacterium tuberculosis</i>

Abstract Innate immune cells, such as monocytes, can generate a non-specific ‘memory’ response (a.k.a. trained immunity) upon stimulation with an antigen/bacterium (e.g., LPS or BCG), which confers heterologous protection against another infectious agent. However, the association between nature of stimulants and corresponding correlate immunity is not fully understood. Similarly, macrophages “trained” by various to subsequent infection different clinical Mycobacterium tuberculosis(Mtb) strains remains unknown. Here, we report profile blood-derived monocytes (BDM) BCG-vaccinated adults monocytic THP-1 cells after BCG, LPS, Purified Protein Derivative (PPD), heat-killed MtbHN878 MtbCDC1551 strains. The these agents Mtb isolates HN878 CDC1551, differ in their virulence potential, was evaluated using standard molecular cellular immunologic assays. BCG- LPS-trained produced higher proinflammatory, antimicrobial responses, autophagy induction than unstimulated, PPD, HK-HN878, CDC1551-stimulated cells. HN878-infected elicited more robust inflammatory CDC1551 infection. A significantly reduced intracellular growth noted BCG augmented adding rapamycin, inducer. similar immunological BDM infected Thus, stimulant affects macrophages’ its Supported grants from NIH (R01 AI161822) Bill Melinda Gates Foundation (INV-009099; formerly OPP1157210).