Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2

Koth, Laura L.; Rodriguez, Madeleine W.; Bernstein, Xin; Chan, Salina; Huang, Xiaozhu; Charo, Israel F.; Rollins, Barrett J.; Erle, David J.

doi:10.1186/1465-9921-5-12

Cited by 33 publications

(24 citation statements)

References 54 publications

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“…Similarly, Aspergillus fumigatus challenge induced enhanced airway inflammation, hyperresponsiveness, and subepithelial fibrosis in CCR2-deficient mice; moreover, CCR2-deficient mice were more susceptible to the injurious effects of an intrapulmonary challenge with live A. fumigatus conidia (19). Mice deficient in CCR2 or its ligand, CCL2/monocyte chemoattractant protein (MCP)-1, developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis in response to Aspergillus antigen challenge (82). Thus, results from these experimental models suggest that CCR2 may have inhibitory effects on the inflammation caused by sensitization with these allergens.…”

Section: Chemokine Receptors In Chronic Lung Diseasesmentioning

confidence: 75%

Chemokine receptors and their therapeutic opportunities in diseased lung: Far beyond leukocyte trafficking

Tománková

Kriegová

Liu

2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Chemokine receptors and their chemokine ligands, key mediators of inflammatory and immune cell trafficking, are involved in the regulation of both physiological and pathological processes in the lung. The discovery that chemokine receptors/chemokines, typically expressed by inflammatory and immune cells, are also expressed in structural lung tissue cells suggests their role in mediating the restoration of lung tissue structure and functions. Thus, chemokine receptors/chemokines contribute not only to inflammatory and immune responses in the lung but also play a critical role in the regulation of lung tissue repair, regeneration, and remodeling. This review aims to summarize current state-of-the-art on chemokine receptors and their ligands in lung diseases such as chronic obstructive pulmonary disease, asthma/allergy, pulmonary fibrosis, acute lung injury, and lung infection. Furthermore, the therapeutic opportunities of chemokine receptors in aforementioned lung diseases are discussed. The review also aims to delineate the potential contribution of chemokine receptors to the processes leading to repair/regeneration of the lung tissue.

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Section: Chemokine Receptors In Chronic Lung Diseasesmentioning

confidence: 75%

Chemokine receptors and their therapeutic opportunities in diseased lung: Far beyond leukocyte trafficking

Tománková

Kriegová

Liu

2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In contrast to those findings, we report here that, even in the absence of MCP-1 gene expression, fibrosis clearly remains evident following infection in adult mice exposed to hyperoxia at birth, as defined by increased collagen staining, increased staining of ␣-sma-expressing myofibroblasts, and increased total collagen protein in the lungs. Similarly, in a mouse model of experimental allergic asthma, airway fibrosis was demonstrated in the absence of MCP-1 or its receptor (26). Given the potential for chemokine redundancy in our model, it is possible that other monocyte chemoattractants could be compensating for the lack of MCP-1 gene expression and contributing to the observed fibrosis in infected mice exposed to hyperoxia at birth.…”

Section: Discussionmentioning

confidence: 97%

Neonatal hyperoxia alters the host response to influenza A virus infection in adult mice through multiple pathways

Buczynski

Yee

Martin

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Exposing preterm infants or newborn mice to high concentrations of oxygen disrupts lung development and alters the response to respiratory viral infections later in life. Superoxide dismutase (SOD) has been separately shown to mitigate hyperoxia-mediated changes in lung development and attenuate virus-mediated lung inflammation. However, its potential to protect adult mice exposed to hyperoxia as neonates against viral infection is not known. Here, transgenic mice overexpressing extracellular (EC)-SOD in alveolar type II epithelial cells are used to test whether SOD can alleviate the deviant pulmonary response to influenza virus infection in adult mice exposed to hyperoxia as neonates. Fibrotic lung disease, observed following infection in wild-type (WT) mice exposed to hyperoxia as neonates, was prevented by overexpression of EC-SOD. However, leukocyte recruitment remained excessive, and levels of monocyte chemoattractant protein (MCP)-1 remained modestly elevated following infection in EC-SOD Tg mice exposed to hyperoxia as neonates. Because MCP-1 is often associated with pulmonary inflammation and fibrosis, the host response to infection was concurrently evaluated in adult Mcp-1 WT and Mcp-1 knockout mice exposed to neonatal hyperoxia. In contrast to EC-SOD, excessive leukocyte recruitment, but not lung fibrosis, was dependent upon MCP-1. Our findings demonstrate that neonatal hyperoxia alters the inflammatory and fibrotic responses to influenza A virus infection through different pathways. Therefore, these data suggest that multiple therapeutic strategies may be needed to provide complete protection against diseases attributed to prematurity and early life exposure to oxygen.

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“…Upon challenge by A. fumigatus, a number of cytokines, including IL-5, IL-6, IL-8, IL-13, and gamma interferon (IFN-␥), and the chemokine monocyte chemotactic protein-1 (MCP-1) have been observed to be induced (46)(47)(48). The role of opsonins in cytokine activation has also been acknowledged, with surfactant protein-D eliciting cytokine responses from A549 cells in response to allergens (49).…”

Section: Discussionmentioning

confidence: 99%

Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species

et al. 2013

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Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A.

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Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2

Cited by 33 publications

References 54 publications

Chemokine receptors and their therapeutic opportunities in diseased lung: Far beyond leukocyte trafficking

Chemokine receptors and their therapeutic opportunities in diseased lung: Far beyond leukocyte trafficking

Neonatal hyperoxia alters the host response to influenza A virus infection in adult mice through multiple pathways

Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species

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