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

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

Nathella Pavan Kumar  1 , Kadar Moideen  1 , Vijay Viswanathan  2 , Shanmugam Sivakumar  3 , Pradeep A Menon  3 , Hardy Kornfeld  4 , Subash Babu  1   5
Affiliations

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

Nathella Pavan Kumar et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Elevated circulating levels of AMPs in PTB-DM and PTB individuals.
The plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin were measured in PTB-DM (n = 44), PTB (n = 44), LTB (n = 30) and NTB (n = 30) individuals. The data are presented as scatter plots with each circle representing a single individual. P values were calculated using the Kruskal—Wallis test with Dunn’s post—hoc for multiple comparisons.
Fig 2
Fig 2. Elevated circulating levels of cathelicidin and HBD2 in bilateral and cavitary disease in PTB-DM individuals and relationship to bacterial burden.
(A) The plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin were measured in PTB-DM individuals with bilateral vs unilateral disease. (B) The plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin were measured in PTB-DM individuals with cavitary vs non-cavitary disease. (C) The relationship between the plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin and smear grades as estimated by sputum smears was examined in PTB-DM individuals. The data are presented as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney test or the Linear trend post—test.
Fig 3
Fig 3. Elevated circulating levels of cathelicidin and HBD2 in bilateral and cavitary disease in PTB individuals and relationship to bacterial burdens.
(A) The plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin were measured in PTB individuals with bilateral vs unilateral disease. (B) The plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin were measured in PTB individuals with cavitary vs non-cavitary disease. (C) The relationship between the plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin and smear grades as estimated by sputum smears was examined in PTB individuals. The data are presented as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney test or the Linear trend post—test.
Fig 4
Fig 4. Significant correlation between circulating levels of AMPs and glycemic parameters in all PTB individuals.
(A) The relationship between the plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin and HbA1c levels was examined in all PTB individuals at baseline (B) The relationship between the plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin and HbA1c levels was examined in all PTB individuals at the end of anti-TB treatment. (C) The relationship between the plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin and fasting blood glucose (FBG) levels was examined in all PTB individuals at baseline. The data are presented as scatter plots with each circle representing a single individual. P values were calculated using the Spearman Rank Correlation.
Fig 5
Fig 5. Altered circulating levels of AMPs at the end of standard anti-tuberculosis therapy in PTB-DM and PTB individuals.
(A) The plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin were measured in PTB-DM individuals at baseline (pre-T) and at 6 months of ATT (post-T). (B) The plasma levels of cathelicidin (LL37), HBD2, HNP1-3 and granulysin were measured in PTB individuals at baseline (pre-T) and at 6 months of ATT (post-T). The data are presented as line graphs with each line representing a single individual. P values were calculated using the Wilcoxon signed rank test.
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