Modulation of dendritic cell and monocyte subsets in tuberculosis-diabetes co-morbidity upon standard tuberculosis treatment

Abstract

Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis (PTB), with development of DM pandemic in countries where tuberculosis (TB) is also endemic. However, the effect of anti-TB treatment on the changes in dentritic cell (DC) and monocyte subset phenotype in TB-DM co-morbidity is not well understood. In this study, we characterized the frequency of DC and monocyte subsets in individuals with PTB with (PTB-DM) or without coincident diabetes mellitus (PTB-NDM) before, during and after completion of anti-TB treatment. PTB-DM is characterized by diminished frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes at baseline and 2 months of anti-TB treatment but not following 6 months of treatment completion in comparison to PTB-NDM. DC and monocyte subsets exhibit significant but borderline correlation with fasting blood glucose and glycated hemoglobin levels. Finally, while minor changes in the DC and monocyte compartment were observed at 2 months of treatment, significantly increased frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes were observed at the successful completion of anti-TB treatment. Our data show that coincident diabetes alters the frequencies of innate subset distribution of DC and monocytes in TB-DM co-morbidity and suggests that most of these changes are reversible following anti-TB therapy.

Figure 1. PTB-DM is associated with altered frequencies of DC subsets at baseline and following treatment

The frequencies of DC subsets in PTB-DM (n=30) and PTBNDM (n=27) individuals at baseline (A) and at two (B) and six (C) months following treatment. The data are represented as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney test.

Figure 2. PTB-DM is associated with altered frequencies of monocyte subsets at baseline and following treatment

The frequencies of monocyte subsets in PTB-DM (n=30) and PTB-NDM (n=27) individuals at baseline (A) and at two (B) and six (C) months following treatment. The data are represented as scatter plots with each circle representing a single individual. P values were calculated using the Mann-Whitney test.

Figure 3. Relationship between DC subsets and hyperglycemia or bacterial burdens in PTB individuals

(A) The correlation between the frequencies of DC subsets and fasting blood glucose levels at baseline in all individuals. (B) The correlation between the frequencies of DC subsets and HbA1c levels at baseline in all individuals. (C) The correlation between the frequencies of DC subsets and bacterial burdens as determined by smear grades (1+, 2+ or 3+) in all individuals. The data are represented as scatter plots with each circle representing a single individual. P values were calculated using the Spearman Rank correlation

Figure 4. Relationship between monocyte cell subsets and hyperglycemia or bacterial burdens in PTB individuals

(A) The correlation between the frequencies of monocyte subsets and fasting blood glucose levels at baseline in all individuals. (B) The correlation between the frequencies of monocyte subsets and HbA1c levels at baseline in all individuals. (C) The correlation between the frequencies of monocyte subsets and bacterial burdens as determined by smear grades (1+, 2+ or 3+) in all individuals. The data are represented as scatter plots with each circle representing a single individual. P values were calculated using the Spearman Rank correlation.

Figure 5. Treatment induced alterations in dendritic cell subsets in PTB individuals

The frequencies of DC subsets in (A) PTB- DM and (B) PTB-NDM individuals before and at 2 and 6 months following anti-TB treatment. The data are represented as line diagrams with each line representing a single individual. P values were calculated using the Wilcoxon signed rank test.

Figure 6. Treatment induced alterations in monocyte subsets in PTB individuals

The frequencies of monocyte subsets in in (A) PTB- DM and (B) PTB-NDM individuals before and at 2 and 6 months following anti-TB treatment. The data are represented as line diagrams with each line representing a single individual. P values were calculated using the Wilcoxon signed rank test.