Altered Ratio of IFN-γ/IL-10 in Patients with Drug Resistant Mycobacterium tuberculosis and HIV- Tuberculosis Immune Reconstitution Inflammatory Syndrome

Keira H Skolimowska,Graeme Meintjes,Kerryn Matthews,Katalin A Wilkinson,Dominique J Pepper,Ronnett Seldon,Robert J Wilkinson,Molebogeng X Rangaka,Yoshihiko Hoshino

doi:10.1371/journal.pone.0046481

Abstract

We have described a clinical relationship between HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) and anti-tubercular drug resistance. Here we studied the immune response of TB-IRIS patients from whom a drug-resistant (n = 11) or drug-susceptible (n = 25) Mycobacterium tuberculosis (MTB) strain was isolated after presenting with TB-IRIS. ELISpot analysis and multiplex cytokine analysis of the supernatant collected from peripheral blood mononuclear cells stimulated overnight with the heat-killed H37Rv MTB laboratory strain was used. Although there was no statistical difference in IFN-gamma ELISpot responses between the two groups, the results point towards higher bacterial load in the drug-resistant patients, possibly due to failed therapy. The ratio between secreted IFN-gamma/IL-10 and IL-2/IL-10 was significantly lower in TB-IRIS patients in whom the cause of TB was a drug-resistant strain compared to those with a fully sensitive strain (p = 0.02). Since host immune responses are dependent on the bacterial load, we hypothesise that the impaired cytokine balance is likely to be caused by the poorly controlled bacterial growth in these patients.

Highlights

Antiretroviral therapy (ART) reduces the risk of tuberculosis (TB) in HIV-1 infected persons by as much as 80% [1,2]
We found that TB-IRIS is associated with hypercytokinemia [16], and hypothesised that there might be a difference in the immune response detectable between TB-IRIS patients with drug-resistant compared to drug-sensitive TB
Because of the opposing trends of the Th1 cytokines and the regulatory IL-10 concentrations observed between the MDR and fully sensitive (FS) groups, we evaluated the ratio of IFN-gamma/IL-10 in Peripheral blood mononuclear cells (PBMC) stimulated with hkH37Rv, and found it to be significantly higher in the FS group compared to the MDR group, p = 0.02 (Figure 2)

Summary

Introduction

Antiretroviral therapy (ART) reduces the risk of tuberculosis (TB) in HIV-1 infected persons by as much as 80% [1,2]. We describe an altered balance between the Th1 and regulatory responses with decreased Th1 (IFN-gamma and IL-2) and increased IL-10 cytokine secretion in TB-IRIS patients in whom the cause of TB was a drug resistant strain compared to those with a sensitive strain.

Results

Conclusion