Dendritic cells are early cellular targets of Listeria monocytogenes after intestinal delivery and are involved in bacterial spread in the host

Abstract

SummaryWe studied the sequence of cellular events leading to the dissemination of Listeria monocytogenes from the gut to draining mesenteric lymph nodes (MLNs) by confocal microscopy of immunostained tissue sections from a rat ligated ileal loop system. OX-62-positive cells beneath the epithelial lining of Peyer's patches (PPs) were the first Listeria targets identified after intestinal inoculation. These cells had other features typical of dendritic cells (DCs): they were large, pleiomorphic and major histocompatibility complex class II hi . Listeria were detected by microscopy in draining MLNs as early as 6 h after inoculation. Some 80±90% of bacteria were located in the deep paracortical regions, and 100% of the bacteria were present in OX-62-positive cells. Most infected cells contained more than five bacteria each, suggesting that they had arrived already loaded with bacteria. At later stages, the bacteria in these areas were mostly present in ED1-positive mononuclear phagocytes. These cells were also infected by an actA mutant defective in cell-to-cell spreading. This suggests that Listeria are transported by DCs from PPs to the deep paracortical regions of draining MLNs and are then transmitted to other cell populations by mechanisms independent of ActA. Another pathway of dissemination to MLNs was identified, probably involving free Listeria and leading to the infection of ED3-positive mononuclear phagocytes in the subcapsular sinus and adjacent paracortical areas. This study provides evidence that DCs are major cellular targets of L. monocytogenes in PPs and that DCs may be involved in the early dissemination of this pathogen. DCs were not sites of active bacterial replication, making these cells ideal vectors of infection.

Intestinal Dendritic Cell Subsets: Differential Effects of Systemic TLR4 Stimulation on Migratory Fate and Activation In Vivo

“…LPS administration had no detectable effect on the number or distribution of DC subsets in rat PP. This lack of response is probably not due to an inherent lack of mobility of PP DC, because others have reported modulation of PP DC migration in response to microbial stimulation in rodents (47)(48)(49). The differences may relate to DC maturity, because, in contrast to lamina propria DC, most PP DC are mature (surface MHC class II high ).…”

The arsenal of virulence factors deployed byListeria monocytogenesto promote its cell infection cycle

“…17 Dendritic cells are also early cellular targets after intestinal delivery, 18 in which L. monocytogenes is able to escape from phagosomes before spreading to neighboring cells. 19,20 Unless its replication is restrained by an efficient host innate immune response, bacteria are able to escape from immune clearance and will keep on multiplying. Host survival is thus dependent on the development of an effective adaptive immune response, which, if not provided, can permit bacteria to re-enter the bloodstream and possibly reach the brain or the placenta, causing potentially fatal systemic infections.…”

Indoleamine 2,3-dioxygenase–expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection

“…A major role of DCs during early enteral L. monocytogenes infection has been recently suggested by immunohistochemical studies in rats (15). DCs phagocytose L. monocytogenes in the small intestine after the bacteria cross the intestinal barrier and are the major cells transporting L. monocytogenes to the draining mesenterical lymph nodes.…”

“…On the other hand, intracellular replication must be tightly controlled in order to prevent destruction of DCs, which would result in both lack of CTL induction and systemic spreading of bacteria. Thus, DCs had to evolve mechanisms controlling the number of viable intracellular L. monocytogenes (15,19,20). For at least one subtype of murine DCs, production of TNF-α and iNOS has been implicated in innate immune functions of DCs (21).…”