Recognition of enteroinvasive Escherichia coli and Shigella flexneri by dendritic cells: distinct dendritic cell activation states

The innate and adaptive immune responses of dendritic cells (DCs) to enteroinvasive Escherichia coli (EIEC) infection were compared with DC responses to Shigella flexneri infection. EIEC triggered DCs to produce interleukin (IL)-10, IL-12 and tumour necrosis factor (TNF)-alpha, whereas S. flexneri induced only the production of TNF-alpha. Unlike S. flexneri, EIEC strongly increased the expression of toll like receptor (TLR)-4 and TLR-5 in DCs and diminished the expression of co-stimulatory molecules that may cooperate to inhibit CD4(+) T-lymphocyte proliferation. The inflammation elicited by EIEC seems to be related to innate immunity both because of the aforementioned results and because only EIEC were able to stimulate DC transmigration across polarised Caco-2 cell monolayers, a mechanism likely to be associated with the secretion of CC chemokine ligands (CCL) 20 and TNF-alpha. Understanding intestinal DC biology is critical to unravelling the infection strategies of EIEC and may aid in the design of treatments for infectious diseases.

Comparative analysis of the pathological events involved in immune and non-immune TRALI models

Background and Objectives Transfusion-related acute lung injury (TRALI) is characterized by leukocyte transmigration and alveolar capillary leakage shortly after transfusion. TRALI pathogenesis has not been fully elucidated. In some cases, the infusion of alloantibodies (immune model), whereas in others the combination of neutrophil priming by proinflammatory molecules with the subsequent infusion of biological response modifiers (BRMs) in the hemocomponent (non-immune model) have been implicated. Our aim was to compare the pathological events involved in TRALI induced by antibodies or BRMs using murine models. Materials and Methods In the immune model, human HNA-2+ neutrophils were incubated in vitro with a monoclonal antibody (anti-CD177, clone 7D8) directed against the HNA-2 antigen and injected i.v. in NOD/SCID mice. In the non-immune model, BALB/c mice were treated with low doses of lipopolysaccharide (LPS) followed by platelet-activating factor (PAF) infusion 2 h later. Forty minutes after PAF administration, or 6 h after neutrophil injection, lungs were isolated and histological analysis, determination of a variety of cytokines and chemokines including keratinocyte-derived chemokine (KC), MIP-2, the interleukins IL-1 beta, IL-6, IL-8 as well as TNFa, cell influx and alveolar capillary leakage were performed. Results In both models, characteristic histological findings of TRALI and an increase in KC and MIP-2 levels were detected. In contrast to the immune model, in the non-immune model, there was a dramatic increase in IL-1 beta and TNFa. However, capillary leakage was only detected if PAF was administrated. Conclusions Regardless of the triggering event(s), KC, MIP-2 and integrins participate in TRALI pathogenesis, whereas PAF is essential for capillary leakage when two events are involved.