Researchers led by Tom HM Ottenhof and Mihai Netea (Joosten et al., 2018), aimed to determine the effect of “trained immunity” on mycobacterial growth, particularly in mycobacterial growth inhibition assays (MGIAs). Researchers focused on trained immunity, as recent studies have shown that epigenetic reprogramming of monocytes may also contribute to protection.
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MGIAs measure the ability of immune cells to inhibit of growth of mycobacteria, such as Mycobacterium bovis from the Bacille Calmette-Guérin (BCG) vaccine or Mycobacterium tuberculosis. Despite, being a useful tool for detecting the capacity of individuals to restrict mycobacterial growth, the underlying immunological mechanisms for bacterial growth in MGIAs are still elusive. Studies have suggested that monocyte/lymphocyte ratios, polyfunctional CD4 T cells and even iron metabolism are associated with mycobacterial growth. However, most of these studies have not conclusively demonstrated the immune mechanisms.
Joosten et al., observed increased mycobacterial growth inhibition in recently M.tb exposed individuals compared to individuals that were either recently BCG vaccinated, latently M.tb infected or TB cases. This increased mycobacterial inhibition was associated with increased proportions of TNF-α, IL-1β and IL-6, cytokines previously associated with trained immunity.
Unlike other studies, researchers observed no association between mycobacterial growth control and Th1-cytokine producing cells. Interestingly, they observed an association between mycobacterial growth inhibition and non-classical CD14=dim monocytes producing CXCL10 (and CXCL9). This reduced mycobacterial growth required the presence of CD4+ central memory and not effector memory bulk T cells. Central memory CD4 T cells, express high proportions of CXCR3, the chemokine receptor for CXCL10, as well as CXCL9 and CXCL11 chemokines. This finding suggests that the CXCL10/CXCR3 axis is critical for BCG control, reflecting a link between innate and adaptive immunity, a hypothesis that still requires validation.
Journal Article: Joosten et al., 2018. Mycobacterial growth inhibition is associated with trained innate immunity. Journal of Clinical Investigations.
Article by Cheleka AM Mpande