Role of tumor necrosis factor alpha in innate resistance to mouse pulmonary infection with Pseudomonas aeruginosa.
In the present study, we have investigated the mechanisms underlying mouse resistance to endobronchial infection with Pseudomonas aeruginosa enmeshed in agar beads. This was done by monitoring macrophage activation-associated gene expression in lung and alveolar cells harvested from resistant (BALB/c) and susceptible (DBA/2, C57BL/6, and A/J) strains of mice over the course of infection with P. aeruginosa. Interleukin-1 alpha, interleukin-1 beta, macrophage inflammatory protein-1 alpha, JE, and tumor necrosis factor alpha (TNF-alpha) mRNA expression levels were up-regulated in all strains of mice during the early phase of the infection. The level of TNF-alpha mRNA expression was increased to a greater extent in resistant BALB/c mice than in susceptible DBA/2, C57BL/6, and A/J strains of mice. This observation paralleled a higher secretion of TNF-alpha into the alveolar space of BALB/c mice at 3 and 6 h postinfection. The concentration of TNF-alpha released in alveoli returned to basal levels within 24 h of infection in mice of all strains, even though the TNF-alpha mRNA expression remained high until 3 days after infection. In vivo treatments with either anti-murine TNF-alpha monoclonal antibodies or with aminoguanidine significantly increased the number of P. aeruginosa bacteria detected in the lungs of resistant mice at 3 days postinfection. Overall, these findings indicate that both TNF-alpha and nitric oxide exert a protective role in response to pulmonary infection with P. aeruginosa.
Gosselin
D
D
McGill Centre for the Study of Host Resistance, Montreal General Hospital Research Institute, Quebec, Canada.
DeSanctis
J
J
Boulé
M
M
Skamene
E
E
Matouk
C
C
Radzioch
D
D
D000818:Animals; D001483:Base Sequence; D007113:Immunity, Innate; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000502:physiology; D011552:Pseudomonas Infections / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide