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bioRxiv · 10.64898/2026.11.03.763869

PIM6 Induces Tolerance and Confers Protection against Mycobacterium tuberculosis in Primary Macrophages

Gower, M. S.·Kleberg, L.·Silva, C. S.·Gilleron, M.·Nigou, J.·Correia-Neves, M.·Sundling, C.·Kallenius, G.
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Abstract

Glycolipids are major components of the mycobacterial cell envelope and play critical roles in host-pathogen interactions. Here we investigate the capacity of the mycobacterial glycolipid phosphatidyl-myo-inositol hexamannosides (PIM6) to modulate innate responsiveness in naive primary human monocytes and monocyte-derived macrophages (MDMs). Monocytes and MDMs prestimulated with PIM6, followed by 5 days of rest, secreted attenuated levels of tumor necrosis factor alpha (TNF-), interleukin 6 (IL-6), and interleukin 10 (IL-10) following LPS challenge. PIM6 pretreatment significantly altered pattern recognition receptor expression through the experimental time course and programmed a tolerized phenotype in myeloid cells independent of TLR2 activity. In an infection challenge with H37Rv Mycobacterium tuberculosis (M.tb), MDMs pretreated with PIM6 secreted decreased levels of TNF- and IL-10 and exhibited early increased bacterial control. Together, these data reveal PIM6 as a complex immunomodulator that tolerizes myeloid cells to subsequent stimuli and exerts direct effects on the control of M.tb infection.

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Gower, M. S., Kleberg, L., Silva, C. S., Gilleron, M., Nigou, J., Correia-Neves, M., Sundling, C., Kallenius, G.. 2026-11-04. PIM6 Induces Tolerance and Confers Protection against Mycobacterium tuberculosis in Primary Macrophages. https://doi.org/10.64898/2026.11.03.763869

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