Toll-like receptor 2 is expressed by alveolar epithelial cells type II and macrophages in the human lung

Droemann, Daniel; Goldmann, Torsten; Branscheid, D.; Clark, Ryan R.; Dalhoff, K; Zabel, P.; Vollmer, Ekkehard

doi:10.1007/s00418-003-0497-4

Cited by 107 publications

(38 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is worth mentioning, however, that NKCC1, which is expressed in both epithelial and endothelial cells, is upregulated in the lung in leptospirosis, serving multiple functions ranging from ion transport, thus contributing to the pathology of pulmonary edema, to regulation of macrophage activation and antimicrobial activity [9] [10]. Additionally, PII may also act as immunoregulatory cells and together with macrophages, express Toll-like receptor 2, making them part of the innate immune defense mechanism [35].…”

Section: Discussionmentioning

confidence: 99%

Human Hemorrhagic Pulmonary Leptospirosis: Pathological Findings and Pathophysiological Correlations

et al. 2013

View full text Add to dashboard Cite

BackgroundLeptospirosis is a re-emerging zoonosis with protean clinical manifestations. Recently, the importance of pulmonary hemorrhage as a lethal complication of this disease has been recognized. In the present study, five human necropsies of leptospirosis (Weil‘s syndrome) with extensive pulmonary manifestations were analysed, and the antibodies expressed in blood vessels and cells involved in ion and water transport were used, seeking to better understand the pathophysiology of the lung injury associated with this disease.Principal FindingsProminent vascular damage was present in the lung microcirculation, with decreased CD34 and preserved aquaporin 1 expression. At the periphery and even inside the extensive areas of edema and intraalveolar hemorrhage, enlarged, apparently hypertrophic type I pneumocytes (PI) were detected and interpreted as a non-specific attempt of clearence of the intraalveolar fluid, in which ionic transport, particularly of sodium, plays a predominant role, as suggested by the apparently increased ENaC and aquaporin 5 expression. Connexin 43 was present in most pneumocytes, and in the cytoplasm of the more preserved endothelial cells. The number of type II pneumocytes (PII) was slightly decreased when compared to normal lungs and those of patients with septicemia from other causes, a fact that may contribute to the progressively low PI count, resulting in deficient restoration after damage to the alveolar epithelial integrity and, consequently, a poor outcome of the pulmonary edema and hemorrhage.ConclusionsPathogenesis of lung injury in human leptospirosis was discussed, and the possibility of primary non-inflammatory vascular damage was considered, so far of undefinite etiopathogenesis, as the initial pathological manifestation of the disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Human Hemorrhagic Pulmonary Leptospirosis: Pathological Findings and Pathophysiological Correlations

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Alveolar epithelial cells type II (AEC-II) may contribute to this Th1-favoring environment, since patient-derived AEC-II produce IL-18 upon TLR-2 stimulation (87, 88). Additionally, AEC-II may contribute to CXCR3 + Th1 cell recruitment by production of CXCL10 (89).…”

Section: Granuloma Formationmentioning

confidence: 99%

Granuloma Formation in Pulmonary Sarcoidosis

et al. 2013

View full text Add to dashboard Cite

Sarcoidosis is a granulomatous disorder of unknown cause, affecting multiple organs, but mainly the lungs. The exact order of immunological events remains obscure. Reviewing current literature, combined with careful clinical observations, we propose a model for granuloma formation in pulmonary sarcoidosis. A tight collaboration between macrophages, dendritic cells, and lymphocyte subsets, initiates the first steps toward granuloma formation, orchestrated by cytokines and chemokines. In a substantial part of pulmonary sarcoidosis patients, granuloma formation becomes an on-going process, leading to debilitating disease, and sometimes death. The immunological response, determining granuloma sustainment is not well understood. An impaired immunosuppressive function of regulatory T cells has been suggested to contribute to the exaggerated response. Interestingly, therapeutical agents commonly used in sarcoidosis, such as glucocorticosteroids and anti-TNF agents, interfere with granuloma integrity and restore the immune homeostasis in autoimmune disorders. Increasing insight into their mechanisms of action may contribute to the search for new therapeutical targets in pulmonary sarcoidosis.

show abstract

“…The binding event triggers an intracellular signalling cascade through dimerisation of the receptor and the subsequent recruitment of signalling proteins, leading to the production of immune mediators such as chemokines and cytokines. Eleven TLRs have been identified in humans located on multiple cell types including neutrophils, macrophages, and epithelial cells [4, 5]. TLR activity is vital for pathogen clearance, but dysregulation can occur which can have severe consequences for the host.…”

Section: Introductionmentioning

confidence: 99%

Mitogen-activated protein kinases (MAPKs) are modulated during Francisella tularensis infection, but inhibition of extracellular-signal-regulated kinases (ERKs) is of limited therapeutic benefit

Saint

D’Elia

Bryant

et al. 2016

Eur J Clin Microbiol Infect Dis

View full text Add to dashboard Cite

Francisella tularensis is a Gram-negative intracellular bacterium that causes the disease tularemia. The disease can be fatal if left untreated and there is currently no licenced vaccine available; the identification of new therapeutic targets is therefore required. Toll-like receptors represent an interesting target for therapeutic modulation due to their essential role in generating immune responses. In this study, we analysed the in vitro expression of the key mitogen-activated protein kinases (MAPKs) p38, JNK and ERK in murine alveolar macrophages during infection with F. tularensis. The phosphorylation profile of ERK highlighted its potential as a target for therapeutic modulation and subsequently the effect of ERK manipulation was measured in a lethal intranasal F. tularensis in vivo model of infection. The selective ERK1/2 inhibitor PD0325901 was administered orally to mice either pre- or post-challenge with F. tularensis strain LVS. Both treatment regimens selectively reduced ERK expression, but only the pre-exposure treatment produced decreased bacterial burden in the spleen and liver, which correlated with a significant reduction in the pro-inflammatory cytokines IFN-γ, MCP-1, IL-6, and TNF-α. However, no overall improvements in survival were observed for treated animals in this study. ERK may represent a useful therapeutic target where selective dampening of the immune response (to control the damaging pathology seen during infection) is combined with antibiotic treatment required to eradicate bacterial infection. This combination treatment strategy has been shown to be effective in other models of tularemia.

show abstract

Toll-like receptor 2 is expressed by alveolar epithelial cells type II and macrophages in the human lung

Cited by 107 publications

References 29 publications

Human Hemorrhagic Pulmonary Leptospirosis: Pathological Findings and Pathophysiological Correlations

Human Hemorrhagic Pulmonary Leptospirosis: Pathological Findings and Pathophysiological Correlations

Granuloma Formation in Pulmonary Sarcoidosis

Mitogen-activated protein kinases (MAPKs) are modulated during Francisella tularensis infection, but inhibition of extracellular-signal-regulated kinases (ERKs) is of limited therapeutic benefit

Contact Info

Product

Resources

About