Murine pulmonary infection with Listeria monocytogenes: differential susceptibility of BALB/c, C57BL/6 and DBA/2 mice.
Murine listeriosis is a paradigm to understand host pathogen interactions. Airway infections with Listeria monocytogenes, although representing a serious problem in early onset neonatal listeriosis, has not been investigated in detail in animal models so far. Here, the susceptibility of BALB/c, DBA/2 and C57BL/6 mice towards an intratracheal (i.t.) infection with virulent L. monocytogenes EGDe and the attenuated variant L. monocytogenes EGD hlyW491A(pERL3-CMVGFP) is reported. The course of infection was characterized by determination of bacterial numbers in the organs and assessment of the health condition of the mice. The distribution and cellular localization of Listeria in the airways was assessed by immunocytochemistry and confocal and electron microscopy. The differential susceptibility of inbred mouse strains to airway infections with L. monocytogenes could be assigned to the major virulence factor listeriolysin O. Resistant C57BL/6 mice were not affected by the two listerial strains. In contrast, BALB/c and DBA/2 mice showed differential susceptibility towards L. monocytogenes EGDe and attenuated bacteria, with all the mice being killed by the wild-type bacteria but rarely by the variant that secretes a listeriolysin of only 10% activity of that of the wild-type toxin. Thus, listeriolysin is a decisive factor for differential susceptibility against Listeria. After i.t. application, bacteria were predominantly localized in the peribronchiolar space and invaded alveolar macrophages but rarely lung epithelial cells. Dissemination from the lung into the deep organs started almost immediately after application, although a pulmonary bacterial reservoir remained during the first 4 days.
Munder
Antje
A
Clinical Research Group OE 6711, Center of Pediatrics, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. munder.antje@mh-hannover.de
Zelmer
Andrea
A
Schmiedl
Andreas
A
Dittmar
Kurt E J
KE
Rohde
Manfred
M
Dorsch
Martina
M
Otto
Klaus
K
Hedrich
Hans-J
HJ
Tümmler
Burkhard
B
Weiss
Siegfried
S
Tschernig
Thomas
T
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006460:Hemolysin Proteins; D008089:Listeria monocytogenes / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D008168:Lung / Q000382:microbiology / Q000648:ultrastructure; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D046529:Microscopy, Electron, Transmission; D013045:Species Specificity
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C038705:hlyA protein, Listeria monocytogenes