Erschienen:
American Society for Microbiology, 2009
Erschienen in:Infection and Immunity
Sprache:
Englisch
DOI:
10.1128/iai.00272-09
ISSN:
0019-9567;
1098-5522
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>ABSTRACT</jats:title><jats:p>In humans with typhoid fever or in mouse strains susceptible to<jats:italic>Salmonella enterica</jats:italic>serovar Typhimurium (<jats:italic>S</jats:italic>. Typhimurium) infection, bacteria gain access to extraintestinal tissues, causing severe systemic disease. Here we show that in the gut-draining mesenteric lymph nodes (MLN), the majority of<jats:italic>S.</jats:italic>Typhimurium-carrying cells show dendritic-cell (DC) morphology and express the DC marker CD11c, indicating that<jats:italic>S</jats:italic>. Typhimurium bacteria are transported to the MLN by migratory DCs. In vivo FLT-3L-induced expansion of DCs, as well as stimulation of DC migration by Toll-like receptor agonists, results in increased numbers of<jats:italic>S</jats:italic>. Typhimurium bacteria reaching the MLN. Conversely, genetically impaired DC migration in chemokine receptor CCR7-deficient mice reduces the number of<jats:italic>S</jats:italic>. Typhimurium bacteria reaching the MLN. This indicates that transport of<jats:italic>S</jats:italic>. Typhimurium from the intestine into the MLN is limited by the number of migratory DCs carrying<jats:italic>S</jats:italic>. Typhimurium bacteria. In contrast, modulation of DC migration does not affect the number of<jats:italic>S</jats:italic>. Typhimurium bacteria reaching systemic tissues, indicating that DC-bound transport of<jats:italic>S</jats:italic>. Typhimurium does not substantially contribute to systemic<jats:italic>S</jats:italic>. Typhimurium infection. Surgical removal of the MLN results in increased numbers of<jats:italic>S</jats:italic>. Typhimurium bacteria reaching systemic sites early after infection, thereby rendering otherwise resistant mice susceptible to fatal systemic disease development. This suggests that the MLN provide a vital barrier shielding systemic compartments from DC-mediated dissemination of<jats:italic>S</jats:italic>. Typhimurium. Thus, confinement of<jats:italic>S</jats:italic>. Typhimurium in gut-associated lymphoid tissue and MLN delays massive extraintestinal dissemination and at the same time allows for the establishment of protective adaptive immune responses.</jats:p>