Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51843 / 66949
mikrobiologie@vetmed.fu-berlin.de
Background and objectives:
Early recognition by the innate immune system iskey for successful defense against Listeria monocytogenes (Lm). Although Lm still represents an important cause of morbidity in the newborn, the precise roles ofToll-like receptors (TLRs) during neonatal listeriosis remains up to date completely unknown.
Materials and methods:
NeonatalC57BL/6 WT as well as TLR9-deficient (TLR9-/-) mice were infected intranasally with Lm. To determine bacterial loads, pups were sacrificed at one and three dayspost infection (dpi) and organs were obtained for replica plating. Tissue tropism and immune responses were analyzed by immunohistochemistry and qRT-PCR.
Results:
We found that bacterial loads in nose, brain, lung, liver and spleen were comparable in neonatal WT and TLR9-/-mice at one dpi. At three dpi, CFU counts in TLR9-/-mice were significantly elevated in all investigated organs and the blood. Additionally, mortality rates of TLR9-/-neonates were strongly increased. As demonstrated by histopathological examination, TLR9-/-pups revealed enlarged and necrotic infection foci in nasal, brain and spleen tissue. Finally, qRT-PCRanalysis showed an increase of various pro-inflammatory as well as neutrophil-and monocyte-attracting cytokine mRNA expression in brain and spleen tissue of TLR9-/-mice.
Conclusion:
We demonstrate for the first time an essential role of TLR9 for innate immunity during systemic and neuronal listeriosis in the newborn mouse after nasal challenge.