Plasma chemokines are biomarkers of disease severity, higher bacterial burden and delayed sputum culture conversion in pulmonary tuberculosis

Nathella P Kumar,Hardy Kornfeld,Subash Babu,Shanmugam Sivakumar,Arul Nancy,Mohan Natarajan,Basavaradhya S Shruthi,Vijay Viswanathan,Kadar Moideen

doi:10.1038/s41598-019-54803-w

Abstract

Plasma cytokines are biomarkers of disease extent and mycobacterial burden in pulmonary tuberculosis (PTB). Whether chemokines can perform the same role in PTB is not known. We examined the plasma levels of chemokines in individuals with PTB, latent TB (LTB) or healthy controls (HC) and their association with disease severity and mycobacterial burdens in PTB. We also examined the chemokines in PTB individuals at the end of anti-tuberculous chemotherapy (ATT). PTB individuals exhibited significantly higher levels of CCL1, CCL3, CXCL1, CXCL2, CXCL9 and CXCL10 in comparison to LTB and/or HC individuals. PTB individuals with bilateral or cavitary disease displayed significantly elevated levels of CCL1, CCL3, CXCL1, CXCL10 and CXCL11 compared to those with unilateral or non-cavitary disease and also exhibited a significant positive relationship with bacterial burdens. In addition, PTB individuals with slower culture conversion displayed significantly elevated levels of CCL1, CCL3, CXCL1 and CXCL9 at the time of PTB diagnosis and prior to ATT. Finally, the chemokines were significantly reduced following successful ATT. Our data demonstrate that PTB is associated with elevated levels of chemokines, which are partially reversed followed chemotherapy. Our data demonstrate that chemokines are markers of disease severity, predicting increased bacterial burden and delayed culture conversion in PTB.

Highlights

Plasma cytokines are biomarkers of disease extent and mycobacterial burden in pulmonary tuberculosis (PTB)
anti-tuberculous chemotherapy (ATT) was given to PTB individuals using the directly observed treatment, short course (DOTS) strategy
Chemokines are major mediators of resistance in TB and these findings are mostly derived from animal models of infection[5]. These data indicate that chemokines can serve as a double - edged sword with both the levels and timing of chemokine production serving as the balance of protection versus pathology[6]

Summary

Introduction

Plasma cytokines are biomarkers of disease extent and mycobacterial burden in pulmonary tuberculosis (PTB). We examined the plasma levels of chemokines in individuals with PTB, latent TB (LTB) or healthy controls (HC) and their association with disease severity and mycobacterial burdens in PTB. PTB individuals with bilateral or cavitary disease displayed significantly elevated levels of CCL1, CCL3, CXCL1, CXCL10 and CXCL11 compared to those with unilateral or non-cavitary disease and exhibited a significant positive relationship with bacterial burdens. Our data demonstrate that chemokines are markers of disease severity, predicting increased bacterial burden and delayed culture conversion in PTB. Our previous work has demonstrated that plasma cytokines are biomarkers of disease severity, mycobacterial burden and slower culture conversion in PTB12. Our data demonstrate that chemokines were markers of disease severity, bacterial burden and time to culture conversion in PTB

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