Granzyme B-expressing neutrophils correlate with bacterial load in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques.

摘要: The role of neutrophils in tuberculosis (TB), and whether express granzyme B (grzB), a pro-apoptotic enzyme associated with cytotoxic T cells, is controversial. We examined peripheral blood (PB) lung granulomas Mycobacterium tuberculosis-infected cynomolgus macaques humans to determine mycobacterial products or pro-inflammatory factors induce neutrophil grzB expression. found large numbers grzB-expressing macaque human these cells contained more grzB+ granules than cells. Higher neutrophil, but not cell, expression correlated increased bacterial load. Although unstimulated PB lacked expression, upon exposure M.tuberculosis bacilli, culture filtrate protein lipopolysaccharide from Escherichia coli. Perforin required for granzyme-mediated cytotoxicity by was observed granuloma neutrophils. Nonetheless, stimulated secreted as determined enzyme-linked immunospot assays. Purified bactericidal bacteriostatic, suggesting acts on extracellular targets, potentially enhancing migration through matrix regulating apoptosis activation other cell types. These data indicate the environment up-regulates suggests previously unappreciated aspect biology TB.