Heightened circulating levels of antimicrobial peptides in tuberculosis—Diabetes co-morbidity and reversal upon treatment

BACKGROUND The association of antimicrobial peptides (AMPs) with tuberculosis-diabetes comorbidity (PTB-DM) is not well understood. METHODS To study the association of AMPs with PTB-DM, we examined the systemic levels of cathelicidin (LL37), human beta defensin- 2 (HBD2), human neutrophil peptides 1-3, (HNP1-3) and granulysin in individuals with either PTB-DM, PTB, latent TB (LTB) or no TB infection (NTB). RESULTS Circulating levels of cathelicidin and HBD2 were significantly higher and granulysin levels were significantly lower in PTB-DM compared to PTB, LTB or NTB, while the levels of HNP1-3 were significantly higher in PTB-DM compared to LTB or NTB individuals. Moreover, the levels of cathelicidin and/or HBD2 were significantly higher in PTB-DM or PTB individuals with bilateral and cavitary disease and also exhibited a significant positive relationship with bacterial burden. Cathelidin, HBD2 and HNP1-3 levels exhibited a positive relationship with HbA1c and/or fasting blood glucose levels. Finally, anti-tuberculosis therapy resulted in significantly diminished levels of cathelicidin, HBD2, granulysin and significantly enhanced levels of HNP1-3 and granulysin in PTB-DM and/or PTB individuals. CONCLUSION Therefore, our data demonstrate that PTB-DM is associated with markedly enhanced levels of AMPs and diminished levels of granulysin.