The impact of Haemophilus ducreyi cytolethal distending toxin on cells involved in immune response

The Haemophilus ducreyi cytolethal distending toxin (HdCDT) induces cell cy cle arrest and thereby inhibits cell proliferation of many cultured mammali an cell-lines. We investigated the effect of HdCDT on circulating human hem atopoietic cells, including T- and B-cells, monocytes and polymorphonuclear cells (PMN). Lymphocytes were stimulated with T- and B-cell specific mitog ens, whereas monocytes and PMN with endotoxin. HdCDT inhibited the mitogen- induced proliferation of T-cells in a dose-dependent manner as assayed by [ H-3]-thymidine incorporation and MTT assays. Similarly to T-cells, HdCDT al so inhibited the proliferation of B-cells and consequently the immunoglobul in production, measured by ELISPOT and ELISA assays. In contrast, the HdCDT did not affect monocytes or PMN, as measured by MTT assay. The TNF-alpha p roduction by monocytes and the phagocytic ability of PMN were neither affec ted. The monocytic cell line THP-1 was, however, sensitive to the toxin, se en as a reduction of proliferation and viability after exposure to HdCDT. I n conclusion, exposure to HdCDT significantly affects the proliferation and other biological activities of stimulated human T- and B-cells, while circ ulating monocytes and PMN are not sensitive to HdCDT. The sensitivity of ce lls of the acquired immune system to HdCDT may hamper specific host respons e to H. ducreyi and contribute to persistence of chancroid lesions. (C) 200 1 Academic Press.