Early bacterial clearance from murine lungs. Species-dependent phagocyte response.

Rehm, S R; Gross, Gary N.; Pierce, Alan K.

doi:10.1172/jci109844

Cited by 121 publications

(58 citation statements)

References 39 publications

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“…Clearance of bacterial pathogens in the lung during infection is mediated primarily via an efficient innate immune response. Although several cell subsets are most likely involved, neutrophils are the most important phagocytic cells for early bacterial clearance in the lung (50). In this context, the present study demonstrates that the recruitment of neutrophils most likely contributes to improved E. coli clearance in TIRAP ϩ/ϩ mice (Fig.…”

Section: Tirapmentioning

confidence: 54%

Toll-IL-1 Receptor Domain-Containing Adaptor Protein Is Critical for Early Lung Immune Responses againstEscherichia coliLipopolysaccharide and ViableEscherichia coli

Jeyaseelan

Manzer

Young³

et al. 2005

The Journal of Immunology

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Pulmonary bacterial diseases are a leading cause of mortality in the U.S. Innate immune response is vital for bacterial clearance from the lung, and TLRs play a critical role in this process. Toll-IL-1R domain-containing adaptor protein (TIRAP) is a key molecule in the TLR4 and 2 signaling. Despite its potential importance, the role of TIRAP-mediated signaling in lung responses has not been examined. Our goals were to determine the role of TIRAP-dependent signaling in the induction of lung innate immune responses against Escherichia coli LPS and viable E. coli, and in lung defense against E. coli in mice. LPS-induced neutrophil sequestration; NF-κB translocation; keratinocyte cell-derived chemokine, MIP-2, TNF-α, and IL-6 expression; histopathology; and VCAM-1 and ICAM-1 expression were abolished in the lungs of TIRAP−/− mice. A cell-permeable TIRAP blocking peptide attenuated LPS-induced lung responses. Furthermore, immune responses in the lungs of TIRAP−/− mice were attenuated against E. coli compared with TIRAP+/+ mice. TIRAP−/− mice also had early mortality, higher bacterial burden in the lungs, and more bacterial dissemination following E. coli inoculation. Moreover, we used human alveolar macrophages to examine the role of TIRAP signaling in the human system. The TIRAP blocking peptide abolished LPS-induced TNF-α, IL-6, and IL-8 expression in alveolar macrophages, whereas it attenuated E. coli-induced expression of these cytokines and chemokines. Taken together, this is the first study illustrating the crucial role of TIRAP in the generation of an effective early immune response against E. coli LPS and viable E. coli, and in lung defense against a bacterial pathogen.

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Section: Tirapmentioning

confidence: 54%

Toll-IL-1 Receptor Domain-Containing Adaptor Protein Is Critical for Early Lung Immune Responses againstEscherichia coliLipopolysaccharide and ViableEscherichia coli

Jeyaseelan

Manzer

Young³

et al. 2005

The Journal of Immunology

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“…Host defense against P. aeruginosa pneumonia is dependent on early neutrophil recruitment (20,21). In contrast, pulmonary defense against S. aureus largely relies on alveolar macrophages, which efficiently clear S. aureus in vivo (20,22). We found the capacity of alveolar macrophages to ingest S. aureus in vivo to be undiminished in MyD88 Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 81%

“…We found the capacity of alveolar macrophages to ingest S. aureus in vivo to be undiminished in MyD88 Ϫ/Ϫ mice. Neutrophils do contribute to pulmonary defense against S. aureus at high bacterial inocula (20,23), and we cannot exclude that MyD88 Ϫ/Ϫ mice might exhibit impaired resistance to higher doses of staphylococci. The ability of MyD88 Ϫ/Ϫ mice to control lung infection with S. aureus contrasts sharply with their marked susceptibility to i.v.…”

Section: Discussionmentioning

confidence: 98%

“…This difference may reflect the different roles for specific phagocytes in resistance to these pathogens. Host defense against P. aeruginosa pneumonia is dependent on early neutrophil recruitment (20,21). In contrast, pulmonary defense against S. aureus largely relies on alveolar macrophages, which efficiently clear S. aureus in vivo (20,22).…”

Section: Discussionmentioning

confidence: 99%

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Cutting Edge: Myeloid Differentiation Factor 88 Is Essential for Pulmonary Host Defense against Pseudomonas aeruginosa but Not Staphylococcus aureus

Skerrett

Liggitt²,

Hajjar

et al. 2004

The Journal of Immunology

162

157

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Myeloid differentiation factor 88 (MyD88) is an adapter molecule required for signal transduction via Toll-like receptors (TLRs) and receptors of the IL-1 family. Consequently, MyD88-deficient mice are highly susceptible to bacterial infections, including systemic infection with Staphylococcus aureus. To determine the role of MyD88 in innate immunity to bacterial pneumonia, we exposed MyD88-deficient and wild-type mice to aerosolized Pseudomonas aeruginosa or S. aureus. As predicted, MyD88-deficient mice failed to mount an early cytokine or inflammatory response or to control bacterial replication after infection with P. aeruginosa, which resulted in necrotizing pneumonia and death. By contrast, MyD88-deficient mice controlled S. aureus infection despite blunted local cytokine and inflammatory responses. Thus, whereas MyD88-dependent signaling is integral to the initiation of cytokine and inflammatory responses to both pathogens following infection of the lower respiratory tract, MyD88 is essential for innate immunity to P. aeruginosa but not S. aureus.

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“…Therefore, infection created an increase in the relative amounts of MU in wild-type mice and, interestingly, of neutrophils in the absence of SHP-1. In comparison, LPS stimulation created the usual [27,28] strong increase in the percentage of neutrophils with a relatively low level of MU in both types of mice. As for absolute numbers at 3 and 6 h post inoculation, SHP-1-deficient mice had significantly more MU, neutrophils and eosinophils recruited in the pouch than their wild-type counterparts (Fig.…”

Section: Tnf-a and Mip-2 Expression In Leishmania Majorinfected Footpadsmentioning

confidence: 85%

Regulation of theLeishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1

et al. 2005

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Modulation of the phagocyte protein tyrosine phosphatase (PTP) SHP-1 by the parasite Leishmania favors its survival and propagation within its mammalian host. In vivo, the absence of SHP-1 leads to virtually absent footpad swelling, accompanied by enhanced inducible nitric oxide synthase expression. In this study, using an air pouch model, we show that viable motheaten SHP-1-deficient mice harbored a stronger inflammatory response against Leishmania infection than wild-type mice. This response was portrayed by higher pro-inflammatory cytokine (TNF-a, IL-1b and IL-6) expression and secretion and by greater chemokine and chemokine receptor expression. These inflammatory molecules were probably responsible for the stronger cellular recruitment, mainly of neutrophils, seen at the site of infection in viable motheaten mice within 6 h post inoculation. We also provide strong evidence that protein tyrosine phosphatases in general, and SHP-1 in particular, are important regulators of chemokine gene expression. Overall, this study suggests that the ability of Leishmania to induce SHP-1 activity in its host allows the taming of an otherwise strong innate inflammatory response that would be detrimental for its survival and progression.

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Early bacterial clearance from murine lungs. Species-dependent phagocyte response.

Cited by 121 publications

References 39 publications

Toll-IL-1 Receptor Domain-Containing Adaptor Protein Is Critical for Early Lung Immune Responses againstEscherichia coliLipopolysaccharide and ViableEscherichia coli

Toll-IL-1 Receptor Domain-Containing Adaptor Protein Is Critical for Early Lung Immune Responses againstEscherichia coliLipopolysaccharide and ViableEscherichia coli

Cutting Edge: Myeloid Differentiation Factor 88 Is Essential for Pulmonary Host Defense against Pseudomonas aeruginosa but Not Staphylococcus aureus

Regulation of theLeishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1

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