Defective Innate Cell Response and Lymph Node Infiltration Specify Yersinia pestis Infection

Unité des Yersinia, Institut Pasteur, Paris, France.
PLoS ONE (Impact Factor: 3.23). 02/2008; 3(2):e1688. DOI: 10.1371/journal.pone.0001688
Source: PubMed


Since its recent emergence from the enteropathogen Yersinia pseudotuberculosis, Y. pestis, the plague agent, has acquired an intradermal (id) route of entry and an extreme virulence. To identify pathophysiological events associated with the Y. pestis high degree of pathogenicity, we compared disease progression and evolution in mice after id inoculation of the two Yersinia species. Mortality studies showed that the id portal was not in itself sufficient to provide Y. pseudotuberculosis with the high virulence power of its descendant. Surprisingly, Y. pseudotuberculosis multiplied even more efficiently than Y. pestis in the dermis, and generated comparable histological lesions. Likewise, Y. pseudotuberculosis translocated to the draining lymph node (DLN) and similar numbers of the two bacterial species were found at 24 h post infection (pi) in this organ. However, on day 2 pi, bacterial loads were higher in Y. pestis-infected than in Y. pseudotuberculosis-infected DLNs. Clustering and multiple correspondence analyses showed that the DLN pathologies induced by the two species were statistically significantly different and identified the most discriminating elementary lesions. Y. pseudotuberculosis infection was accompanied by abscess-type polymorphonuclear cell infiltrates containing the infection, while Y. pestis-infected DLNs exhibited an altered tissue density and a vascular congestion, and were typified by an invasion of the tissue by free floating bacteria. Therefore, Y. pestis exceptional virulence is not due to its recently acquired portal of entry into the host, but is associated with a distinct ability to massively infiltrate the DLN, without inducing in this organ an organized polymorphonuclear cell reaction. These results shed light on pathophysiological processes that draw the line between a virulent and a hypervirulent pathogen.

14 Reads
  • Source
    • "On cellular level, it is known that in bubonic plague Pla enables bacterial dissemination from the skin to the lymph nodes where Y. pestis multiplies and causes swollen lymphs, or buboes (Sodeinde et al., 1992). Guinet et al. (2008) observed that bacterial loads of Pla-positive Y. pestis became higher than those of wild type (i.e., Pla-deficient) Y. pseudotuberculosis in rat lymph nodes at 24–48 h after infection when also significant histopathological changes were evident. They concluded that Y. pseudotuberculosis infection induced an organized leukocyte response that was not seen with Y. pestis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The outer membrane protease Pla belongs to the omptin protease family spread by horizontal gene transfer into Gram-negative bacteria that infect animals or plants. Pla has adapted to support the life style of the plague bacterium Yersinia pestis. Pla has a β-barrel fold with 10 membrane-spanning β strands and five surface loops, and the barrel surface contains bound lipopolysaccharide (LPS) that is critical for the conformation and the activity of Pla. The biological activity of Pla is influenced by the structure of the surface loops around the active site groove and by temperature-induced LPS modifications. Several of the putative virulence-related functions documented for Pla in vitro address control of the human hemostatic system, i.e., coagulation and fibrinolysis. Pla activates human plasminogen to the serine protease plasmin and activates the physiological plasminogen activator urokinase. Pla also inactivates the protease inhibitors alpha-2-antiplasmin and plasminogen activator inhibitor 1 (PAI-1) and prevents the activation of thrombin-activatable fibrinolysis inhibitor (TAFI). These functions enhance uncontrolled fibrinolysis which is thought to improve Y. pestis dissemination and survival in the mammalian host, and lowered fibrin(ogen) deposition has indeed been observed in mice infected with Pla-positive Y. pestis. However, Pla also inactivates an anticoagulant, the tissue factor (TF) pathway inhibitor, which should increase fibrin formation and clotting. Thus, Pla and Y. pestis have complex interactions with the hemostatic system. Y. pestis modifies its LPS upon transfer to the mammalian host and we hypothesize that the contrasting biological activities of Pla in coagulation and fibrinolysis are influenced by LPS changes during infection.
    Frontiers in Cellular and Infection Microbiology 07/2013; 3:35. DOI:10.3389/fcimb.2013.00035 · 3.72 Impact Factor
  • Source
    • "Three outbred CD-1 mice (Charles River Laboratory Inc., Wilmington, MA, USA) were injected intradermally per time point in the ear as previously described [19]. For all inoculations, mice were anesthetized using isofluorane (inhalation administration) and ketamine (IP injection). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Scrub typhus is an important endemic disease of the Asia-Pacific region caused by Orientia tsutsugamushi. To develop an effective vaccine to prevent scrub typhus infection, a better understanding of the initial host-pathogen interaction is needed. The objective of this study was to investigate early bacterial dissemination in a CD-1 Swiss outbred mouse model after intradermal injection of O. tsutsugamushi. Three human pathogenic strains of O. tsutsugamushi (Karp, Gilliam, and Woods) were chosen to investigate the early infection characteristics associated with bacterial virulence. Tissue biopsies of the intradermal injection site and draining lymph nodes were examined using histology and immunohistochemistry to characterize bacterial dissemination, and correlated with quantitative real-time PCR for O. tsutsugamushi in blood and tissue from major organs. Soluble adhesion molecules were measured to examine cellular activation in response to infection. No eschar formation was seen at the inoculation site and no clinical disease developed within the 7 day period of observation. However, O. tsutsugamushi was localized at the injection site and in the draining lymph nodes by day 7 post inoculation. Evidence of leukocyte and endothelial activation was present by day 7 with significantly raised levels of sL-selectin, sICAM-1 and sVCAM-1. Infection with the Karp strain was associated with earlier and higher bacterial loads and more extensive dissemination in various tissues than the less pathogenic Gilliam and Woods strains. The bacterial loads of O. tsutsugamushi were highest in the lungs and spleens of mice inoculated with Karp and Gilliam, but not Woods strains. Strains of higher virulence resulted in more rapid systemic infection and dissemination in this model. The CD-1 mouse intradermal inoculation model demonstrates features relevant to early scrub typhus infection in humans, including the development of regional lymphadenopathy, leukocyte activation and distant organ dissemination after low-dose intradermal injection with O. tsutsugamushi.
    PLoS ONE 01/2013; 8(1):e54570. DOI:10.1371/journal.pone.0054570 · 3.23 Impact Factor
  • Source
    • "This finding suggests that T3SS encoded by pCD1/pYV plasmid is responsible for the immune repression induced by Y. pestis (Comer et al., 2010). However, no difference is detected in mice subcutaneously challenged with Y. pestis or Y. pseudotuberculosis during the progression of the infection to the draining lymph nodes (before 2 days of infection) (Guinet et al., 2008). The subsequent Y. pseudotuberculosis infection induces massive PMN influx and the bacterial replication is contained, whereas PMN infiltration is absent in the Y. pestis-infected draining lymph nodes, which are typified by an invasion of the tissue by free-floating bacteria. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Omics has remarkably changed the way we investigate and understand life. Omics differs from traditional hypothesis-driven research because it is a discovery-driven approach. Mass datasets produced from omics-based studies require experts from different fields to reveal the salient features behind these data. In this review, we summarize omics-driven studies to reveal the virulence features of Yersinia pestis through genomics, trascriptomics, proteomics, interactomics, etc. These studies serve as foundations for further hypothesis-driven research and help us gain insight into Y. pestis pathogenesis.
    Frontiers in Cellular and Infection Microbiology 12/2012; 2:157. DOI:10.3389/fcimb.2012.00157 · 3.72 Impact Factor
Show more

Similar Publications

Preview (3 Sources)

14 Reads
Available from