Mycobacterial 65-kD heat shock protein induces release of proinflammatory cytokines from human monocytic cells

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Abstract
Monocytes having phagocytosed mycobacteria are known to present the bacterial 65‐kD heat shock protein (hsp) on their cell surface to αβ and γδ T lymphocytes. Cytotoxic CD4+ cells may then lyse monocytes expressing mycobacterial 65‐kD hsp. However, it is not known whether 65‐kD hsp directly stimulates monocyte functions other than antigen presentation. This study has demonstrated that following extraction of bacterial lipopolysaccharide, purified recombinant mycobacterial 65‐kD hsp may directly activate THP‐1 cells, a human monocytic line, to accumulate mRNA for and secrete tumour necrosis factor (TNF), a cytokine important in granuloma formation, the characteristic host immune response to mycobacterial infection. TNF gene expression and secretion following stimulation by hsp was dose‐dependent and abolished by heat‐induced proteolysis. Subsequently, THP‐1 cells secreted IL‐6 and IL‐8, cytokines involved in recruitment and differentiation of T lymphocytes. The data indicate that secretion of proinflammatory cytokines from monocytes activated by mycobacterial 65‐kD hsp may be important in the host immune response and in the development of antigen‐specific T cell‐mediated immunity.