Influence of HTLV-1 on the clinical, microbiologic and immunologic presentation of tuberculosis

Abstract

Background: HTLV-1 is associated with increased susceptibility to Mycobacterium tuberculosis infection and severity of tuberculosis. Although previous studies have shown that HTLV-1 infected individuals have a low frequency of positive tuberculin skin test (TST) and decreasing in lymphoproliferative responses compared to HTLV-1 uninfected persons, these studies were not performed in individuals with history of tuberculosis or evidence of M. tuberculosis infection. Therefore the reasons why HTLV-1 infection increases susceptibility to infection and severity of tuberculosis are not understood.The aim of this study was to evaluate how HTLV-1 may influence the clinical, bacteriologic and immunologic presentation of tuberculosis.

Methods: The study prospectively enrolled and followed 13 new cases of tuberculosis associated with HTLV-1 (cases) and 25 patients with tuberculosis without HTLV-1 infection (controls). Clinical findings, bacterial load in the sputum, x-rays, immunological response and death were compared in the two groups.

Results: There were no differences in the demographic, clinical and TST response between the two study groups. IFN-γ and TNF-α production was higher in unstimulated cultures of mononuclear cells of case than in control patients (p < 0.01). While there was no difference in IFN-γ production in PPD stimulated cultures, TNF-α levels were lower in cases than in controls (p = 0.01). There was no difference in the bacterial load among the groups but sputum smear microscopy results became negative faster in cases than in controls. Death only occurred in two co-infected patients.

Conclusion: While the increased susceptibility for tuberculosis infection in HTLV-1 infected subjects may be related to impairment in TNF-α production, the severity of tuberculosis in co-infected patients may be due to the enhancement of the Th1 inflammatory response, rather than in their decreased ability to control bacterial growth.

Figure 1

Survival analysis of sputum smear conversion for acid-fast bacilli during tuberculosis treatment. Tuberculosis patients with and without HTLV-1 infection, who remained test positive by acid-fast bacilli (AFB) smear microscopy after 10 and 20 days of tuberculosis treatment were evaluated with Kaplan-Meier survival estimates.

Figure 2

TNF-α and IFN-γ production with or without stimulus with PPD. TNF-α and IFN-γ production was determined by ELISA in supernatants of PBMC culture from co-infected patients and patients with tuberculosis only unstimulated (A and C) or stimulated with PPD (B and D). Results of PPD stimulated cultures represent values subtracted from the IFN-γ production in unstimulated cultures.

Figure 3

Expression of mRNA for IL-12 and IFN-γ production after exogenous addition of PPD plus IL-12. mRNA for IL-12 was determined by RT-PCR in unstimulated cultures of PBMC from seronegative healthy subjects, co-infected patients, and patients with tuberculosis only (A). IFN-γ production was evaluated by ELISA in supernatants of PBMC cultures unstimulated or stimulated with PPD and PPD plus IL-12 in the concentration of 50 μg/ml (B and C).