CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.

Zahra Hasan, Aga Khan University
Jacqueline M Cliff
Hazel M Dockrell
Bushra Jamil, Aga Khan University
Muhammad Irfan, Aga Khan University
Mussarat Ashraf, Aga Khan University
Rabia Hussain, Aga Khan University


Background: Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNgamma, TNFalpha and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity. Methodology: We investigated live M. tuberculosis- and M. bovis BCG-induced peripheral blood mononuclear cell responses in Patients with tuberculosis (TB) and healthy endemic controls (ECs, n = 36). TB Patients comprised pulmonary (PTB, n = 34) and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16) or severe disseminated ETB (D-ETB, n = 16). Secretion of CCL2, IFNgamma, IL10 and CCL3, and mRNA expression of CCL2, TNFalpha, CCL3 and CXCL8 were determined.


M. tuberculosis- and BCG-induced CCL2 secretion was significantly increased in both PTB and D-ETB (pConclusion: The increased CCL2 and TNFalpha in PTB Patients may support effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is associated with severity of TB, possibly due to increased systemic inflammation found in severe disseminated TB or due to increased monocyte infiltration to lung parenchyma in pulmonary disease.