Effect of tracheal cytotoxin from Bordetella pertussis on human neutrophil function in vitro

Abstract

The infiltration of neutrophils which phagocytose and kill microorganisms is an important defense mechanism against infections of the airways. Bordetella pertussis is a human respiratory pathogen which colonizes ciliated epithelium, causing whooping cough. We have investigated the effects of the peptidoglycan fragment tracheal cytotoxin (TCT) of B. pertussis on human neutrophil function in vitro. TCT (10-6 to 10-8 M) was toxic for human neutrophils, as measured by lactate dehydrogenase release and levels of intracellular ATP. TCT (10-9 to 10-'5 M) did not stimulate neutrophil migration or chemiluminescence and did not affect neutrophil phagocytosis. Incubation of neutrophils for 20 min with TCT (10-9 to 10-1 M) significantly inhibited (P < 0.05) their subsequent migration toward the chemotactic factor N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 10-9 M). Incubation of neutrophils for 20 min with TCT (10-9 to lo-'5 M) significantly inhibited (P < 0.05) chemiluminescence stimulated by FMLP (10-5 M). TCT (10-6 to 10-12 M) did not stimulate interleukin-1 alpha production by neutrophils or serum complement activation by the alternate pathway. We conclude that TCT at concentrations of <10-8 M affects important neutrophil functions and at higher concentrations is toxic. TCT may therefore contribute to the survival of B. pertussis within the airways in vivo.

Pertussis: a matter of immune modulation

“…It is likely that the Ptx-mediated decrease in chemokine release also contributed to the reduced early infiltration of leukocytes observed in earlier studies (Meade et al, 1985;Spangrude et al, 1985). In addition to Ptx, TCT has also been shown to inhibit neutrophil chemotaxis, at least in vitro (Cundell et al, 1994), which may also partially contribute to this effect.…”

Mini‐review: The role of peptidoglycan recognition in innate immunity

“…In addition, peptidoglycan from Gram‐positive bacteria induces meningeal inflammation in rabbits injected intracisternally 4. In cell culture models, early reports identified the immunomodulatory properties of peptidoglycan and/or subfragments of peptidoglycan towards monocytes, macrophages 5, 6, neutrophils 7 and respiratory epithelial cells 8. Pro‐inflammatory cytokines such as IL‐1, IL‐6 and TNF‐α are known to be released by macrophages following exposure to either Gram‐positive bacterial peptidoglycan or soluble muramyl peptides derived from polymeric peptidoglycan (for a review, see 9).…”

Mammalian NLR proteins; discriminating foe from friend

“…82,83 This hypothesis was later confirmed in the pioneering studies of Rosenthal, Goldman and others, who demonstrated the toxic effects of these soluble peptidoglycan fragments on host cells. [84][85][86][87][88] The Gram-negative bacterial pathogens, Neisseria gonorrhoea and Bordetella pertussis, were subsequently shown to release tetra and tri forms of mDAP-containing fragments into the external milieu. 84,[86][87][88] We now know that these forms are specifically recognized by mouse and human forms of NOD1, respectively.…”

“…[84][85][86][87][88] The Gram-negative bacterial pathogens, Neisseria gonorrhoea and Bordetella pertussis, were subsequently shown to release tetra and tri forms of mDAP-containing fragments into the external milieu. 84,[86][87][88] We now know that these forms are specifically recognized by mouse and human forms of NOD1, respectively. 9 Interestingly, much later reports described the IL-8inducing activities of cell-free supernatants of the pathogens, Campylobacter jejuni 89 and Pseudomonas aeruginosa, 90 on non-phagocytic cells.…”