Neonatal host defense mechanisms against Listeria monocytogenes infection: the role of lipopolysaccharides and interferons.
The human newborn infant is susceptible to lethal infection caused by a number of bacterial species including Listeria monocytogenes, a gram-positive rod which is pathogenic by virtue of its ability to survive intracellularly. In adult animals interferon (IFN)-alpha/beta and IFN-gamma or agents that induce or augment IFN production confer protection against lethal L. monocytogenes infection. Regulation and production of IFN is poorly understood during the neonatal period. We therefore evaluated the role of IFN-alpha/beta and IFN-gamma, IFN-inducers (polyinosinic:polycytidylic acid, amino-bromo-phenyl-pyrimidinone, amino-iodophenyl pyrimidinone) and lipopolysaccharide in modifying neonatal L. monocytogenes infection. Pretreatment of juvenile rats with polyinosinic:polycytidylic acid or lipopolysaccharide protected them against a lethal challenge with L. monocytogenes. Among newborn rats, polyinosinic:polycytidylic acid, amino-iodo-phenyl pyrimidinone and amino-bromophenyl-pyrimidinone gave significant protection, however, lipopolysaccharide did not influence survival. The role of IFN was further examined. Pretreatment of 3-d-old rats with purified IFN-alpha/beta, native rat IFN-gamma or rDNA rat IFN-gamma protected them against the lethality of subsequent L. monocytogenes injection. At 3 d after bacterial challenge, bacterial content in the spleens of 3-d-old rats pretreated with rIFN-gamma were significantly decreased compared to controls: IFN-alpha/beta-pretreated animals had less of a decrease, which become significant only 5 d after challenge. Our experiments indicate a role for IFN in neonatal host defense against L. monocytogenes infection.
Bortolussi
R
R
Department of Pediatrics, Dalhousie University, Halifax, Canada.
Issekutz
T
T
Burbridge
S
S
Schellekens
H
H
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000187:drug effects; D007369:Interferon Inducers / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008088:Listeriosis / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains
D007369:Interferon Inducers; D008070:Lipopolysaccharides; D007372:Interferons