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

PLoS One. 2017 Sep 14;12(9):e0184753. doi: 10.1371/journal.pone.0184753. eCollection 2017.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Antigens, Differentiation, T-Lymphocyte / blood
  • Antimicrobial Cationic Peptides / blood*
  • Antitubercular Agents / therapeutic use*
  • Cathelicidins / blood
  • Comorbidity
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / metabolism
  • Young Adult
  • alpha-Defensins / blood*
  • beta-Defensins / blood

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Antimicrobial Cationic Peptides
  • Antitubercular Agents
  • Cathelicidins
  • DEFB4A protein, human
  • GNLY protein, human
  • alpha-Defensins
  • beta-Defensins
  • human neutrophil peptide 1

Grants and funding

This work was jointly sponsored by the Indian Department of Biotechnology; the Indian Council of Medical Research; and the National Institute for Allergy and Infectious Diseases, National Institutes of Health, and administered by CRDF Global [grant USB1-31149-XX-13]. This work was also funded in part by the Division of Intramural Research, NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.