Associations between lipid mediators and cytokine production at different stages of MTB infection

Abstract

Tuberculosis (TB) remains a major health issue worldwide. Similarly to cytokine signalling lipid mediators of inflammation play a key role during the innate and adaptive response to Mycobacterium tuberculosis (MTB).

Aim: To evaluate the dynamics of lipid mediators at different stages of MTB infection in association with cytokine secretion.

Materials and methods: Blood samples from patients with latent TB (LTB, n=9), active TB (ATB, n=11) and IGRA-negative recent contacts of ATB (RC, n=10) were analyzed after 18h PHA stimulation. The levels of lipoxin A4 (LXA4) and prostaglandin 2 (PGE2) were determined by ELISA (SunRed Tech). Concentrations of IL-2, IL-4, IL-6, IL-10, IL-17, IFN-ɣ, and TNF-α were measured by CBA kit (FACSCanto II, FCAParray v3.0).

Results: To evaluate the relative contribution of LXA4 and PGE2 we looked at the PGE2/LXA4 ratio in the studied groups. Unlike LXA4, PGE2 levels varied considerably in RC and ATB but not in LTB. Therefore PGE2 low (L) vs.PGE2 high (H) subgroups were separately analyzed. PGE2/LXA4 ratios in ATB-L and RC-L were comparable to those in LTB (1.2 and 1.3vs1.1, p>0.05). Low PGE2/LXA4 in RC was associated with decreased IL-17 and IL-10 expression (880 and 2800vs2100 and 12400 pg/ml, P<0.05), at the expense of TNFα and IL-6. On the other hand, ATB-L was characterized with elevated IL-10 and lower IL-6 levels as compared to ATB-H (502vs256 and 16700vs21000 pg/ml respectively).

Conclusion: A changing PGE2/LXA4 balance that shapes differently the cytokine background may confer protective immunity to MTB. An optimal immune inflammation associated with lower PGE2 is required at the early stage of infection, while containment of ATB relies on increased PGE2 and reversal of immune activation.

Acknowledgement: Supported by research grant No13/1/14.12.2017, BNSF