Oral Transmission of <em>Listeria monocytogenes</em> in Mice via Ingestion of Contaminated Food

L. monocytogenes are facultative intracellular bacterial pathogens that cause food borne infections in humans. Very little is known about the ...

university of kentucky 

Intestinal Listeria monocytogenes infection is not efficient in mice and this has been attributed to a low affinity interaction between the bacterial surface protein InlA and E-cadherin on murine intestinal epithelial cells. Previous studies using either transgenic mice expressing human E-cadherin or mouse-adapted L. monocytogenes expressing a modified InlA protein (InlA(m)) with high affinity for murine E-cadherin showed increased efficiency of intragastric infection. However, the large inocula used in these studies disseminated to the spleen and liver rapidly, resulting in a lethal systemic infection that made it difficult to define the natural course of intestinal infection. We describe here a novel mouse model of oral listeriosis that closely mimics all phases of human disease: (1) ingestion of contaminated food, (2) a distinct period of time during which L. monocytogenes colonize only the intestines, (3) varying degrees of systemic spread in susceptible vs. resistant mice, and (4) late stage spread to the brain. Using this natural feeding model, we showed that the type of food, the time of day when feeding occurred, and mouse gender each affected susceptibility to L. monocytogenes infection. Co-infection studies using L. monocytogenes strains that expressed either a high affinity ligand for E-cadherin (InlA(m)), a low affinity ligand (wild type InlA from Lm EGDe), or no InlA (Î”inlA) showed that InlA was not required to establish intestinal infection in mice. However, expression of InlA(m) significantly increased bacterial persistence in the underlying lamina propria and greatly enhanced dissemination to the mesenteric lymph nodes. Thus, these studies revealed a previously uncharacterized role for InlA in facilitating systemic spread via the lymphatic system after invasion of the gut mucosa.

InlA promotes dissemination of Listeria monocytogenes to the mesenteric lymph nodes during food borne infection of mice.

L&#39;infection intestinale Listeria monocytogenes n&#39;est pas efficace chez les souris, et ceci a &eacute;t&eacute; attribu&eacute; &agrave; une interaction faible affinit&eacute; entre la prot&eacute;ine bact&eacute;rienne de surface InlA et la E-cadh&eacute;rine sur les cellules &eacute;pith&eacute;liales intestinales murines. &Eacute;tudes ant&eacute;rieures, en utilisant soit des souris transg&eacute;niques exprimant la E-cadh&eacute;rine ou souris adapt&eacute;s L. monocytogenes exprimant une prot&eacute;ine modifi&eacute;e de l&#39;InlA (InlA(m)) avec une forte affinit&eacute; pour murin Qu&#39;e-cadh&eacute;rine a montr&eacute; une efficacit&eacute; accrue de l&#39;infection gastrique. Cependant, les grands inoculums utilis&eacute;es dans ces &eacute;tudes diffus&eacute;s &agrave; la rate et le foie rapidement, entra&icirc;nant une infection syst&eacute;mique l&eacute;tale qui rendait difficile de d&eacute;finissent l&#39;&eacute;volution naturelle de l&#39;infection intestinale. Nous d&eacute;crivons ici un mod&egrave;le de souris roman de list&eacute;riose orale qui imite &eacute;troitement toutes les phases de la maladie humaine: (1) l&#39;ingestion d&#39;aliments contamin&eacute;s, (2) une p&eacute;riode distincte au cours de laquelle L. monocytogenes coloniser uniquement l&#39;intestins, (3) des degr&eacute;s de syst&eacute;mique r&eacute;pandue dans sensibles vs souris r&eacute;sistantes et (4) vers la fin de sc&egrave;ne propagation vers le cerveau. &Agrave; l&#39;aide de ce mod&egrave;le d&#39;alimentation naturel, nous avons montr&eacute; que le type d&#39;aliment, le temps du jour o&ugrave; l&#39;alimentation s&#39;est produite, et sexe de souris chaque touch&eacute; de susceptibilit&eacute; &agrave; l&#39;infection de L. monocytogenes. &Eacute;tudes de co-infection par L. monocytogenes souches qui expriment soit un ligand de haute affinit&eacute; pour la E-cadh&eacute;rine (InlA(m)), un ligand de faible affinit&eacute; (type sauvage InlA de Lm EGDe) ou aucun InlA (&Delta;inlA) a montr&eacute; que la InlA n&#39;&eacute;tait pas tenu d&#39;&eacute;tablir une infection intestinale chez les souris. Toutefois, l&#39;expression de InlA(m) a consid&eacute;rablement augment&eacute; bact&eacute;rienne persistance dans la lamina propria sous-jacente et de la diffusion am&eacute;lior&eacute;e vers les ganglions lymphatiques m&eacute;sent&eacute;riques. Ainsi, ces &eacute;tudes ont r&eacute;v&eacute;l&eacute; un r&ocirc;le non d&eacute;finie auparavant pour l&#39;InlA en facilitant la diffusion syst&eacute;mique par le syst&egrave;me lymphatique apr&egrave;s l&#39;invasion de la muqueuse de l&#39;intestin.

InlA favorise la diffusion de Listeria monocytogenes dans les ganglions lymphatiques m&eacute;sent&eacute;riques au cours de l&#39;infection des souris d&#39;origine alimentaire.

Intestinale infezioni di Listeria monocytogenes non sono efficace nei topi, e questo &egrave; stato attribuito a un&#39;interazione di bassa affinit&agrave; tra la proteina di superficie batterica InlA ed E-caderina su cellule epiteliali intestinali murine. Precedenti studi utilizzando sia topi transgenici che esprimono umana E-caderina o mouse adattato L. monocytogenes che esprime una proteina di InlA modificata (InlA(m)) con alta affinit&agrave; per E-caderina ha mostrato maggiore efficienza di infezione intragastrico murino. Tuttavia, i grandi inoculi utilizzati in questi studi diffusi rapidamente, alla milza e fegato in un letale infezione sistemica che ha reso difficile definiscono il corso naturale dell&#39;infezione intestinale. Descriviamo qui un modello del mouse romanzo di listeriosi orale che imita molto attentamente tutte le fasi della malattia umana: (1) l&#39;ingestione di alimenti contaminati, (2) un distinto periodo di tempo durante il quale L. monocytogenes colonizzare solo l&#39;intestino, (3) diversi gradi di sistemica diffusa in sensibili vs topi resistenti e (4) tarda fase di diffusione al cervello. Utilizzando questo modello di alimentazione naturale, abbiamo dimostrato che il tipo di cibo, il tempo del giorno in cui alimentazione si &egrave; verificato, e genere del mouse ogni interessato suscettibilit&agrave; all&#39;infezione da L. monocytogenes. Gli studi di coinfezione utilizzando L. monocytogenes ceppi che esprime sia un ligando ad alta affinit&agrave; per E-caderina (no InlA, un ligando di bassa affinit&agrave; (wild type InlA da Lm EGDe) o InlA(m)) (&Delta;inlA) ha mostrato che InlA non era necessario stabilire infezione intestinale nei topi. Tuttavia, espressione di InlA(m) significativamente aumentata persistenza batterica nella sottostante lamina propria e notevolmente migliorata diffusione ai linfonodi mesenterici. Cos&igrave;, questi studi hanno rivelato un ruolo precedentemente atipiche per InlA nel facilitare la diffusione sistemica tramite il sistema linfatico dopo l&#39;invasione della mucosa intestinale.

Grant S. Jones

Department of Microbiology,
Immunology,
and Molecular Genetics,
Department of Microbiology, Immunology, and Molecular Genetics

university of kentucky

Oral Transmission of Listeria monocytogenes in Mice via Ingestion of Contaminated Food

Grant S. Jones

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Microbiology,Immunology,and Molecular Genetics,Department of Microbiology, Immunology, and Molecular Genetics

university of kentucky

Oral Transmission of Listeria monocytogenes in Mice via Ingestion of Contaminated Food

Department of Microbiology,
Immunology,
and Molecular Genetics,
Department of Microbiology, Immunology, and Molecular Genetics