Endotoxin Augmented Antigen-Induced Th1 Cell Trafficking Amplifies Airway Neutrophilic Inflammation

Mikhak, Zamaneh; Farsidjani, Alireza; Luster, Andrew D.

doi:10.4049/jimmunol.0803522

Cited by 16 publications

(11 citation statements)

References 44 publications

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“…The LPS challenge increased the percentage of Th1 lymphocytes as well as the production of the main cytokines involved in the Th1 response (IFNg and IL-12). These cells play a critical role in orchestrating host defense against pathogens and in the pathogenesis of many immune-mediated diseases (25). LPS stimulated the Th1 cell trafficking into the airways, thereby confirming the observation made by Mikhak et al (25), and the Th1 cells then amplified the neutrophil inflammatory response initiated by LPS in the airway.…”

Section: Discussionsupporting

confidence: 71%

Dietary Plasma Proteins Modulate the Adaptive Immune Response in Mice with Acute Lung Inflammation

Maijó

Miró

Polo

et al. 2012

The Journal of Nutrition

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We examined the effects of oral plasma protein supplements on the pulmonary adaptive immune response in mice challenged with intranasal LPS. C57BL/6 mice were fed a control diet or a diet supplemented with plasma proteins [spray-dried plasma (SDP) 80 g/kg] or with an Ig concentrate [(IC) 20 g/kg] from postnatal d 19 (weaning) until d 34. Mice were challenged with PBS or LPS from Escherichia coli at d 33 and killed 24 h later for leukocyte analyses or at d 34 and killed 6 h later for cytokine determination. LPS induced the activation of T helper (Th) lymphocytes in lung and blood and this response was reduced by SDP and IC (P < 0.05). In both tissues, LPS increased the Th1 and Th2 subpopulations and this effect was inhibited by the two plasma protein supplements (P < 0.05). The LPS challenge increased the expression of all the cytokines studied (P < 0.01). SDP and IC reduced the expression of IFNγ, IL-5, IL-12p40, IL-12p70, IL-13, and IL-17 in both tissues, whereas they increased the percentage of regulatory Th lymphocytes in lung, even in PBS-treated mice (P < 0.05). LPS reduced the concentration of mature TGFβ1 (P < 0.05) in the lung but did not modify the expression of IL-10. Mice exposed to LPS and supplemented with SDP or IC showed an increased expression of the anti-inflammatory cytokine IL-10 (P < 0.05). Moreover, the two supplements increased the concentration of IL-10 in intestinal mucosa (P < 0.05). Our results show that plasma supplementation reduces the immune response that characterizes the acute lung inflammation syndrome.

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Section: Discussionsupporting

confidence: 71%

Dietary Plasma Proteins Modulate the Adaptive Immune Response in Mice with Acute Lung Inflammation

Maijó

Miró

Polo

et al. 2012

The Journal of Nutrition

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“…Previous studies have noted the presence of NK cells in the lung (Farah et al, 2001; Mikhak et al, 2009), and their accumulation in response to inflammation and injury (Basse et al, 1992). However, the dynamic trafficking of NK cells in response to innate injury such as acute acid-induced lung injury has not been previously reported.…”

Section: Resultsmentioning

confidence: 99%

Leukocyte compartments in the mouse lung: Distinguishing between marginated, interstitial, and alveolar cells in response to injury

Barletta

Cagnina

Wallace

et al. 2012

Journal of Immunological Methods

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We developed a flow cytometry-based assay to simultaneously quantify multiple leukocyte populations in the marginated vascular, interstitial, and alveolar compartments of the mouse lung. An intravenous injection of a fluorescently labeled anti-CD45 antibody was used to label circulating and marginated vascular leukocytes. Following vascular flushing to remove non-adherent cells and collection of broncho-alveolar lavage (BAL) fluid, lungs were digested and a second fluorescent anti-CD45 antibody was added ex vivo to identify cells not located in the vascular space. In the naïve mouse lung, we found about 11 million CD45+ leukocytes, of which 87% (9.5 million) were in the vascular marginated compartment, consisting of 17% NK cells, 17% neutrophils, 57% mononuclear myeloid cells (monocytes, macrophage precursors and dendritic cells), and 10% T cells (CD4+, CD8+, and invariant NKT cells). Non-vascular compartments including the interstitial compartment contained 7.7 × 105 cells, consisting of 49% NK cells, 25% dendritic cells, and 16% other mononuclear myeloid cells. The alveolar compartment was overwhelmingly populated by macrophages (5.63 × 105 cells, or 93%). We next studied leukocyte margination and extravasation into the lung following acid injury, a model of gastric aspiration. At 1 hour after injury, neutrophils were markedly elevated in the blood while all other circulating leukocytes declined by an average of 79 percent. At 4 hours after injury, there was a peak in the numbers of marginated neutrophils, NK cells, CD4+ and CD8+ T cells and a peak in the number of alveolar NK cells. Most interstitial cells consisted of DCs, neutrophils, and CD4+ T cells, and most alveolar compartment cells consisted of macrophages, neutrophils, and NK cells. At 24 hours after injury, there was a decline in the number of all marginated and interstitial leukocytes and a peak in alveolar neutrophils. In sum, we have developed a novel assay to study leukocyte margination and trafficking following pulmonary inflammation and show that marginated cells comprise a large fraction of lung leukocytes that increases shortly after lung injury. This assay may be of interest in future studies to determine if leukocytes become activated upon adherence to the endothelium, and have properties that distinguish them from interstitial and circulating cells.

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“…Further, the presence of LPS during an initial antigen exposure changed the mechanism and magnitude of T-cell trafficking upon subsequent LPS-free antigen challenge, as well as amplified the phagocytic inflammatory response (37). These studies suggest that the response to the LPS-protein mixture in vesicles may translate to protective downstream T-cell and memory responses.…”

mentioning

confidence: 89%

Naturally Produced Outer Membrane Vesicles fromPseudomonas aeruginosaElicit a Potent Innate Immune Response via Combined Sensing of Both Lipopolysaccharide and Protein Components

2010

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Pseudomonas aeruginosa is a prevalent opportunistic human pathogen that, like other Gram-negative pathogens, secretes outer membrane vesicles. Vesicles are complex entities composed of a subset of envelope lipid and protein components that have been observed to interact with and be internalized by host cells. This study characterized the inflammatory responses to naturally produced P. aeruginosa vesicles and determined the contribution of vesicle Toll-like receptor (TLR) ligands and vesicle proteins to that response. Analysis of macrophage responses to purified vesicles by real-time PCR and enzyme-linked immunosorbent assay identified proinflammatory cytokines upregulated by vesicles. Intact vesicles were shown to elicit a profoundly greater inflammatory response than the response to purified lipopolysaccharide (LPS). Both TLR ligands LPS and flagellin contributed to specific vesicle cytokine responses, whereas the CpG DNA content of vesicles did not. Neutralization of LPS sensing demonstrated that macrophage responses to the protein composition of vesicles required the adjuvantlike activity of LPS to elicit strain specific responses. Protease treatment to remove proteins from the vesicle surface resulted in decreased interleukin-6 and tumor necrosis factor alpha production, indicating that the production of these specific cytokines may be linked to macrophage recognition of vesicle proteins. Confocal microscopy of vesicle uptake by macrophages revealed that vesicle LPS allows for binding to macrophage surfaces, whereas vesicle protein content is required for internalization. These data demonstrate that macrophage sensing of both LPS and protein components of outer membrane vesicles combine to produce a bacterial strain-specific response that is distinct from those triggered by individual, purified vesicle components.The innate immune response to Gram-negative bacteria is dominated by recognition of lipopolysaccharide (LPS). LPS is sensed by the Toll-like receptor 4 (TLR4) complex, and numerous studies have focused on both how LPS sensitivity drives effective inflammatory responses, leading to the clearance of infection, as well as how uncontrolled TLR4 signaling can lead to LPS toxicity and play a role in septic shock (20,39,48

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Endotoxin Augmented Antigen-Induced Th1 Cell Trafficking Amplifies Airway Neutrophilic Inflammation

Cited by 16 publications

References 44 publications

Dietary Plasma Proteins Modulate the Adaptive Immune Response in Mice with Acute Lung Inflammation

Dietary Plasma Proteins Modulate the Adaptive Immune Response in Mice with Acute Lung Inflammation

Leukocyte compartments in the mouse lung: Distinguishing between marginated, interstitial, and alveolar cells in response to injury

Naturally Produced Outer Membrane Vesicles fromPseudomonas aeruginosaElicit a Potent Innate Immune Response via Combined Sensing of Both Lipopolysaccharide and Protein Components

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