MYCOBACTERIUM-TUBERCULOSIS ALTERS EXPRESSION OF ADHESION MOLECULES ONMONOCYTIC CELLS

The host response to Mycobacterium tuberculosis is characterized by in teractions between mononuclear cells, with recruitment and fusion of t hese cells culminating in granuloma formation. In addition, the host r esponse to M. tuberculosis requires CD4(+) T-cell reactivity, mediated by antigen-independent as well as antigen-dependent mechanisms. Thus, ,ve hypothesized that cell adhesion molecules such as intercellular ad hesion molecule 1 (ICAM-1; CD54) would participate in the response to infection with M. tuberculosis. Exposure of THP-1 cells derived from a monocyte/macrophage cell line to M. tuberculosis (1:1 bacterium/cell ratio) elicited a sustained increase (660% +/- 49% above resting level ) in the expression of ICAM-1 that continued for at least 72 h. Neithe r the expression of vascular cell adhesion molecule 1 (VCAM-1; CD106) nor that of the integrins lymphocyte function-associated antigen 1 (LF A-1; CD11a/CD18) or CR3 (CD11b/CD18) was increased to a similar extent at corresponding time points. The increase in ICAM-1 protein expressi on was accompanied by an increase in steady-state mRNA (Northern [RNA] analysis). Neutralizing monoclonal antibodies directed against tumor necrosis factor alpha but not interleukin la or interleukin 1 beta sub stantially abrogated the response to M. tuberculosis consistent with a paracrine or autocrine response. Continuous upregulation of the expre ssion of ICAM-1 on mononuclear phagocytes induced by M. tuberculosis m ay mediate the recruitment of monocytes and enhance the antigen presen tation of M. tuberculosis, thus permitting the generation and maintena nce of the host response.