Defective antigen presentation by Mycobacterium tuberculosis-infected monocytes

Abstract

In this study we investigated the effect of an in vitro infection with Mycobacterium tuberculosis on the ability of human monocytes to present the soluble antigen tetanus toxoid to T cells. We observed that tetanus toxoid-specific T-cell proliferation was markedly reduced when monocytes were infected with large numbers (bacterium-to-monocyte ratio, 50:1) of both viable and heat-killed mycobacteria. The level of antigen-induced gamma interferon release also was decreased when M. tuberculosis-containing monocytes were used as antigen-presenting cells. However, mycobacterium-infected monocytes did not show or trigger suppressive activity, because the presence of mycobacterium-infected monocytes did not affect the T-cell response induced by tetanus toxoid-pulsed control monocytes. When M. tuberculosis-infected monocytes were fixed with paraformaldehyde, they were not able to serve as antigen-presenting cells even in the presence of untreated accessory monocytes. Moreover, the uptake of both viable and heat-killed M. tuberculosis cells reduced the expression of human leukocyte antigen DR on monocytes. With regard to accessory function, monocytes infected with large numbers of mycobacteria were less efficient as accessory cells than were control monocytes in cultures of T cells activated with pokeweed mitogen. These results indicate that infection with large numbers of M. tuberculosis cells impairs the ability of monocytes to process and/or present soluble antigen and to serve as accessory cells in T-cell activation.