Innate immunity in the human lung: pathogen recognition and lung disease

Rohmann, K; Tschernig, Thomas; Pabst, Reinhard; Goldmann, Torsten; Drömann, Daniel

doi:10.1007/s00441-010-1048-7

Cited by 28 publications

(18 citation statements)

References 45 publications

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“…In contrast, professional immune cells, especially alveolar macrophages and supported by type II epithelial cells, are located in the alveoli and with their PRRs they can rapidly recognize the PAMPs of pathogens being inhaled or aspirated to the periphery of the lungs [3,4,16,17]. The initiated inflammation follows within few hours, primarily with recruitment of PMNs, and influx of humoral factors such as complement, defensins and cytokines, as the alveolar lumen and vascular lumen is within a distance of a few mm.…”

Section: Discussionmentioning

confidence: 99%

“…The initiated inflammation follows within few hours, primarily with recruitment of PMNs, and influx of humoral factors such as complement, defensins and cytokines, as the alveolar lumen and vascular lumen is within a distance of a few mm. In chronic infection, IgG synthesized in the medulla of the regional lymph nodes and the bone marrow, and induced by different subsets of CD11B high and CD11B -cDCs and pDCs induced by danger signals via the alveolar macrophages and type II alveolar epithelial cells, will also be present in the airway lumen resulting in opsonin activation of PMNs and complement activation, thereby further enhancing inflammation [6,7,15,16,17].…”

Section: Discussionmentioning

confidence: 99%

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Bead-size directed distribution of Pseudomonas aeruginosa results in distinct inflammatory response in a mouse model of chronic lung infection

Christophersen

Trøstrup

Damlund

et al. 2012

Clinical and Experimental Immunology

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SummaryChronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is characterized by biofilms, tolerant to antibiotics and host responses. Instead, immune responses contribute to the tissue damage. However, this may depend on localization of infection in the upper conductive or in the peripheral respiratory zone. To study this we produced two distinct sizes of small alginate beads (SB) and large beads (LB) containing P. aeruginosa. In total, 175 BALB/c mice were infected with either SB or LB. At day 1 the quantitative bacteriology was higher in the SB group compared to the LB group (P < 0·003). For all time-points smaller biofilms were identified by Alcian blue staining in the SB group (P < 0·003). Similarly, the area of the airways in which biofilms were identified were smaller (P < 0·0001). A shift from exclusively endobronchial to both parenchymal and endobronchial localization of inflammation from day 1 to days 2/3 (P < 0·05), as well as a faster resolution of inflammation at days 5/6, was observed in the SB group (P < 0·03). Finally, both the polymorphonuclear neutrophil leucocyte (PMN) mobilizer granulocyte colony-stimulating factor (G-CSF) and chemoattractant macrophage inflammatory protein-2 (MIP-2) were increased at day 1 in the SB group (P < 0·0001). In conclusion, we have established a model enabling studies of host responses in different pulmonary zones. An effective recognition of and a more pronounced host response to infection in the peripheral zones, indicating that increased lung damage was demonstrated. Therefore, treatment of the chronic P. aeruginosa lung infection should be directed primarily at the peripheral lung zone by combined intravenous and inhalation antibiotic treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bead-size directed distribution of Pseudomonas aeruginosa results in distinct inflammatory response in a mouse model of chronic lung infection

Christophersen

Trøstrup

Damlund

et al. 2012

Clinical and Experimental Immunology

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“…Since innate immunity plays a critical role in orchestrating interaction between different host cells, and those cells and the pathogen, modulation of the response through PRR may afford the means to enhance immunity against viruses. The pattern recognition receptors including TLRs appear to be modulated by the presence of pathogens [88].…”

Section: The Role Of Toll-like Receptors In Innate Responsesmentioning

confidence: 99%

Cell mediated innate responses of cattle and swine are diverse during foot-and-mouth disease virus (FMDV) infection: A unique landscape of innate immunity

Toka

Golde

2013

Immunology Letters

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Pathogens in general and pathogenic viruses in particular have evolved a myriad of mechanisms to escape the immune response of mammalian species. Viruses that cause acute disease tend to bear characteristics that make them very contagious, as survival does not derive from chronicity of infection, but spread of disease throughout the herd. Foot-and-mouth disease virus (FMDV) is one of the most contagious viruses known. Upon infection of susceptible species, cloven-hoofed animals, the virus proliferates rapidly and causes a vesicular disease within 2-4 days. Disease symptoms resolve by 10 days to 2 weeks and in most cases, virus can no longer be detected. Periods of fever and viremia are usually brief, 1-3 days. In vivo control of virus infection and clearance of the virus during and following acute infection is of particular interest. The interaction of this virus with cells mediating the early, innate immune response has been analyzed in a number of recent studies. In most reports, the virus has a distinct inhibitory effect on the response of cells early in infection. Here we review these new data and discuss the dynamics of the interaction of virus with different cell types mediating the immune response to infection.

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“…The inflammatory response after NTHi infection has been characterized by the upregulation of proinflammatory cytokines like IL-1β, CXCL-2 and TNF-α which is mediated by activation of mitogen-activated protein kinases (MAPK) and NFκB through Toll-like receptor (TLR) signaling. In addition recent findings suggest the involvement of other pattern recognition receptors (PRRs), in particular NOD-like receptors (NLR) in airway inflammation [4], [5].…”

Section: Introductionmentioning

confidence: 99%

Nontypeable Haemophilus Influenzae Infection Upregulates the NLRP3 Inflammasome and Leads to Caspase-1-Dependent Secretion of Interleukin-1β — A Possible Pathway of Exacerbations in COPD

et al. 2013

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Rationale Nontypeable Haemophilus influenzae (NTHi) is the most common cause for bacterial exacerbations in chronic obstructive pulmonary disease (COPD). Recent investigations suggest the participation of the inflammasome in the pathomechanism of airway inflammation. The inflammasome is a cytosolic protein complex important for early inflammatory responses, by processing Interleukin-1β (IL-1β) to its active form.ObjectivesSince inflammasome activation has been described for a variety of inflammatory diseases, we investigated whether this pathway plays a role in NTHi infection of the airways.MethodsA murine macrophage cell line (RAW 264.7), human alveolar macrophages and human lung tissue (HLT) were stimulated with viable or non-viable NTHi and/or nigericin, a potassium ionophore. Secreted cytokines were measured with ELISA and participating proteins detected via Western Blot or immunohistochemistry.Measurements and Main ResultsWestern Blot analysis of cells and immunohistochemistry of lung tissue detected the inflammasome key components NLRP3 and caspase-1 after stimulation, leading to a significant induction of IL-1β expression (RAW: control at the lower detection limit vs. NTHi 505±111pg/ml, p<0.01). Inhibition of caspase-1 in human lung tissue led to a significant reduction of IL-1β and IL-18 levels (IL-1β: NTHi 24 h 17423±3198pg/ml vs. NTHi+Z-YVAD-FMK 6961±1751pg/ml, p<0.01).ConclusionOur data demonstrate the upregulation of the NRLP3-inflammasome during NTHi-induced inflammation in respiratory cells and tissues. Our findings concerning caspase-1 dependent IL-1β release suggest a role for the inflammasome in respiratory tract infections with NTHi which may be relevant for the pathogenesis of bacterial exacerbations in COPD.

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Innate immunity in the human lung: pathogen recognition and lung disease

Cited by 28 publications

References 45 publications

Bead-size directed distribution of Pseudomonas aeruginosa results in distinct inflammatory response in a mouse model of chronic lung infection

Bead-size directed distribution of Pseudomonas aeruginosa results in distinct inflammatory response in a mouse model of chronic lung infection

Cell mediated innate responses of cattle and swine are diverse during foot-and-mouth disease virus (FMDV) infection: A unique landscape of innate immunity

Nontypeable Haemophilus Influenzae Infection Upregulates the NLRP3 Inflammasome and Leads to Caspase-1-Dependent Secretion of Interleukin-1β — A Possible Pathway of Exacerbations in COPD

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