Research Article: CCL2 Responses to Mycobacterium tuberculosis Are Associated with Disease Severity in Tuberculosis

Date Published: December 29, 2009

Publisher: Public Library of Science

Author(s): Zahra Hasan, Jacqueline M. Cliff, Hazel M. Dockrell, Bushra Jamil, Muhammad Irfan, Mussarat Ashraf, Rabia Hussain, T. Mark Doherty.

Abstract: Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNγ, TNFα 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.

Partial Text: Tuberculosis (TB) causes 1.8 million deaths annually with 9.27 million incident cases of which the majority (55%) are in Asia [1]. Although the primary disease remains at pulmonary sites, extrapulmonary disease is common especially in high TB burden settings [2], [3] or where there is a high rate of human immunodeficiency virus (HIV) co-prevalence [4].

The hematological characteristics of patients and controls included in the study are provided in Table 2, with each group shown separately. While BCG vaccination is administered at birth as part of the National Expanded Immunization Program in the country its coverage is at best up to 70% [33]. Therefore, we also documented the presence of a BCG scar in subjects to determine whether they had a history of BCG vaccination. TB transmission rates in the country are high with an incidence of 181/100,000 therefore only the TST- EC group can be considered as un-infected by M. tuberculosis. The TST+ EC group is also clinically healthy but it not possible to assess whether their positive tuberculin reaction is attributable to BCG vaccination or exposure to environmental mycobacteria or even M. tuberculosis. Hence we have considered TST+ and TST- ECs separately.

Our data illustrates differences in the activation of immune regulatory chemokines and cytokines in tuberculosis disease with differing site and severity. CCL2 has potent chemotactic and activating properties for monocytes, macrophages, dendritic cells and CD4+ T cells. The most significant finding was that CCL2 was consistently associated with severe disease. We propose that CCL2 could be a useful adjunct marker of severity in tuberculosis.



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