Mice That Overexpress CC Chemokine Ligand 2 in Their Lungs Show Increased Protective Immunity to Infection with<i>Mycobacterium bovis</i>Bacille Calmette‐Guérin

Schreiber, Olivia; Steinwede, Kathrin; Ding, Nadine; Srivastava, Mrigank; Maus, Regina; Länger, Florian; Prokein, J.; Ehlers, Stefan; Welte, Tobias; Gunn, Michael D.; Maus, Ulrich A.

doi:10.1086/591501

Cited by 19 publications

(21 citation statements)

References 26 publications

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“…Previous reports demonstrated that CCL2 was upregulated during infectious (42) and noninfectious lung injury (5,10,41,52). CCL2 has been showed to induce leukocyte infiltration during inflammation (8,38,39,43). Overexpression of human CCL2 in alveolar type II epithelial cells elicited a substantial recruitment of monocytic cells into both parenchymal and alveolar compartments of mouse lungs in the absence of lung inflammation (19).…”

Section: Discussionmentioning

confidence: 99%

“…inflammation resolution; apoptosis; acute lung injury ACCUMULATION OF LEUKOCYTES at sites of inflammation is essential for host defense during inflammation. CC chemokine ligand-2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 have been well documented for their ability to induce leukocyte infiltration during inflammation (8,19,38,39,43). Studies have shown that CCL2 is elevated in various pulmonary diseases, including chronic obstructive pulmonary disease (10), asthma (47), and interstitial lung diseases such as idiopathic pulmonary fibrosis and systemic sclerosis (30,31,44).…”

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confidence: 99%

“…The proper activation of the immune system combats infections and tissue injury. For example, overexpression of CCL2 protected mice from bacterial acute lung injury by promoting monocyte infiltration (39,43,51). Blockade of CCR2 by administration of anti-CCR2 antibody to Streptococcus pneumoniae-infected mice led to progressive lung inflammation with impaired leukocyte recruitment (51).…”

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confidence: 99%

“…Overexpression of CCL2 improves bacterium clearance in mice (39,43,51). Deficiency in CCL2 in mice led to an increased bacterial burden or viral load following Pseudomonas aeruginosa (25) or influenza (12).…”

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confidence: 99%

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A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury

Liang¹,

Jung²,

Tighe³

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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CC chemokine ligand-2 (CCL2)/monocyte chemoattractant protein (MCP)-1 expression is upregulated during pulmonary inflammation, and the CCL2-CCR2 axis plays a critical role in leukocyte recruitment and promotion of host defense against infection. The role of CCL2 in mediating macrophage subpopulations in the pathobiology of noninfectious lung injury is unknown. The goal of this study was to examine the role of CCL2 in noninfectious acute lung injury. Our results show that lung-specific overexpression of CCL2 protected mice from bleomycin-induced lung injury, characterized by significantly reduced mortality, reduced neutrophil accumulation, and decreased accumulation of the inflammatory mediators IL-6, CXCL2 (macrophage inflammatory protein-2), and CXCL1 (keratinocyte-derived chemokine). There were dramatic increases in the recruitment of myosin heavy chain (MHC) II IA/IEintCD11cintcells, exudative macrophages, and dendritic cells in Ccl2 transgenic mouse lungs both at baseline and after bleomycin treatment compared with levels in wild-type mice. We further demonstrated that MHCII IA/IEintCD11cintcells engulfed apoptotic cells during acute lung injury. Our data suggested a previously undiscovered role for MHCII IA/IEintCD11cintcells in apoptotic cell clearance and inflammation resolution.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury

Liang¹,

Jung²,

Tighe³

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…+ mononuclear phagocyte subsets as well as lymphocyte subsets isolated from lung parenchyma and lung dLN were immunophenotypically analyzed according to their cell surface Ag expression profiles, as described previously (24,25). First, the respective CD11c + mononuclear phagocyte subsets purified from lung homogenates of CG/NE-deficient and wild-type mice were gated according to their forward light scatter ( …”

Section: Cd11cmentioning

confidence: 99%

Cathepsin G and Neutrophil Elastase Contribute to Lung-Protective Immunity against Mycobacterial Infections in Mice

Steinwede

Maus

Bohling

et al. 2012

The Journal of Immunology

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The neutrophil serine proteases cathepsin G (CG) and neutrophil elastase (NE) are involved in immune-regulatory processes and exert antibacterial activity against various pathogens. To date, their role and their therapeutic potential in pulmonary host defense against mycobacterial infections are poorly defined. In this work, we studied the roles of CG and NE in the pulmonary resistance against Mycobacterium bovis bacillus Calmette-Guérin (BCG). CG-deficient mice and even more pronounced CG/NE-deficient mice showed significantly impaired pathogen elimination to infection with M. bovis BCG in comparison to wild-type mice. Moreover, granuloma formation was more pronounced in M. bovis BCG-infected CG/NE-deficient mice in comparison to CG-deficient and wild-type mice. A close examination of professional phagocyte subsets revealed that exclusively neutrophils shuttled CG and NE into the bronchoalveolar space of M. bovis BCG-infected mice. Accordingly, chimeric wild-type mice with a CG/NE-deficient hematopoietic system displayed significantly increased lung bacterial loads in response to M. bovis BCG infection. Therapeutically applied human CG/NE encapsulated in liposomes colocalized with mycobacteria in alveolar macrophages, as assessed by laser scanning and electron microscopy. Importantly, therapy with CG/NE-loaded liposomes significantly reduced mycobacterial loads in the lungs of mice. Together, neutrophil-derived CG and NE critically contribute to deceleration of pathogen replication during the early phase of antimycobacterial responses. In addition, to our knowledge, we show for the first time that liposomal encapsulated CG/NE exhibit therapeutic potential against pulmonary mycobacterial infections. These findings may be relevant for novel adjuvant approaches in the treatment of tuberculosis in humans.

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Monocyte-derived Inflammatory Dendritic Cells in the Granuloma During Mycobacterial Infection

Schreiber

Sándor

2011

Advances in Experimental Medicine and Biology

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The monocyte-derived, inflammatory dendritic cell subset plays an important role during immune responses against infections. This review will focus on the complex, changing role of this subset during mycobacterial infection. Studies demonstrate that in addition to sustaining a systemic anti-mycobacterial response, the inflammatory dendritic cell subset present in Mycobacterium-induced granulomas also influences local immune regulation within the granuloma over the course of infection. This review will also survey the literature on how similar and different inflammatory dendritic cell subsets during other infections.

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Mice That Overexpress CC Chemokine Ligand 2 in Their Lungs Show Increased Protective Immunity to Infection withMycobacterium bovisBacille Calmette‐Guérin

Abstract: The data of the current study suggest that CCL2-dependent amplification of endogenous host-defense programs in the lung may improve the lungs' protective immunity against mycobacterial infections.

Cited by 19 publications

References 26 publications

A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury

A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury

Cathepsin G and Neutrophil Elastase Contribute to Lung-Protective Immunity against Mycobacterial Infections in Mice

Monocyte-derived Inflammatory Dendritic Cells in the Granuloma During Mycobacterial Infection

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