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The pulmonary innate immune system is heavily implicated in the perpetual airway inflammation and impaired host defense characterizing Chronic Obstructive Pulmonary Disease (COPD). The airways of patients suffering from COPD are infiltrated by various immune and inflammatory cells including macrophages, neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages, neutrophils and T lymphocytes is well characterized, the contribution of dendritic cells to COPD pathogenesis is still the subject of emerging research. A paper by Botelho and colleagues in the current issue of Respiratory Research investigates the importance of dendritic cell recruitment in cigarette-smoke induced acute and chronic inflammation in mice. Dendritic cells of the healthy lung parenchyma and airways perform an important sentinel function and regulate immune homeostasis. During inflammatory responses the function and migration pattern of these cells is dramatically altered but the underlying mechanisms are incompletely understood. Botelho and colleagues demonstrate here the importance of IL-1R1/IL-1α related mechanisms including CCL20 production in cigarette-smoke induced recruitment of dendritic cells and T cell activation in the mouse lung. [ABSTRACT FROM AUTHOR]

Background: Diffuse alveolar damage (DAD), which is the histological surrogate for acute respiratory distress syndrome (ARDS), has a multifactorial aetiology. Therefore it is possible that the immunopathology differs among the various presentations of DAD. The aim of this study is to compare lung immunopathology of viral (influenza A(H1N1)pdm09) to non-viral, extrapulmonary aetiologies in autopsy cases with DAD.Methods: The lung tissue of 44 patients, was divided in the H1N1 group (n = 15) characterized by severe pulmonary injury due to influenza A(H1N1)pdm09 infection; the ARDS group (n = 13), characterized by patients with DAD due to non-pulmonary causes; and the Control group (n = 16), consisting of patients with non-pulmonary causes of death. Immunohistochemistry and image analysis were used to quantify, in the parenchyma and small airways, several immune cell markers.Results: Both DAD groups had higher expression of neutrophils and macrophages in parenchyma and small airways. However, there was a higher expression of CD4+ and CD8+ T lymphocytes, CD83+ dendritic cells, granzyme A+ and natural killer + cell density in the lung parenchyma of the H1N1 group (p < 0.05). In the small airways, there was a lower cell density of tryptase + mast cells and dendritic + cells and an increase of IL-17 in both DAD groups (p < 0.05).Conclusion: DAD due to viral A(H1N1)pdm09 is associated with a cytotoxic inflammatory phenotype, with partially divergent responses in the parenchyma relative to the small airways. In non-viral DAD, main immune cell alterations were found at the small airway level, reinforcing the role of the small airways in the pathogenesis of the exudative phase of DAD. [ABSTRACT FROM AUTHOR]

Background: The integrin CD11c is known as a marker for dendritic cells and has recently been described on T cells following lymphotropic choriomeningitis virus infection, a systemic infection affecting a multitude of organs. Here, we characterise CD11c bearing T cells in a murine model of localised pulmonary infection with respiratory syncytial virus (RSV). Methods: Mice were infected intranasally with RSV and expression of β2 integrins and T lymphocyte activation markers were monitored by flow cytometry. On day 8 post RSV infection CD11c+ CD8+ and CD11c- CD8+ T cells were assessed for cytokine production, cytotoxic activity and migration. Expression of CD11c mRNA in CD8+ T cells was assessed by quantitative PCR. Results: Following RSV infection CD11c+ CD8+ T cells were detectable in the lung from day 4 onwards and accounted for 45.9 ± 4.8% of CD8+ T cells on day 8 post infection, while only few such cells were present in mediastinal lymph nodes, spleen and blood. While CD11c was virtually absent from CD8+ T cells in the absence of RSV infection, its mRNA was expressed in CD8+ T cells of both naïve and RSV infected mice. CD11c+, but not CD11c-, CD8+ T cells showed signs of recent activation, including up-regulation of CD11a and expression of CD11b and CD69 and were recruited preferentially to the lung. In addition, CD11c+ CD8+ T cells were the major subset responsible for IFNγ production, induction of target cell apoptosis in vitro and reduction of viral titres in vivo. Conclusion: CD11c is a useful marker for detection and isolation of pulmonary antiviral cytotoxic T cells following RSV infection. It identifies a subset of activated, virus-specific, cytotoxic T cells that exhibit potent antiviral effects in vivo. [ABSTRACT FROM AUTHOR]