Abstract
Transforming growth factor β (TGF-β) regulates inflammation, immunosuppression, and wound-healing cascades, but it remains unclear whether any of these functions involve regulation of myeloid cell function. The present study demonstrates that selective deletion of TGF-βRII expression in myeloid phagocytes i) impairs macrophage-mediated suppressor activity, ii) increases baseline mRNA expression of proinflammatory chemokines/cytokines in the lung, and iii) enhances type 2 immunity against the hookworm parasite Nippostrongylus brasiliensis. Strikingly, TGF-β-responsive myeloid cells promote repair of hookworm-damaged lung tissue, because LysM(Cre)TGF-βRII(flox/flox) mice develop emphysema more rapidly than wild-type littermate controls. Emphysematous pathology in LysM(Cre)TGF-βRII(flox/flox) mice is characterized by excessive matrix metalloprotease (MMP) activity, reduced lung elasticity, increased total lung capacity, and dysregulated respiration. Thus, TGF-β effects on myeloid cells suppress helminth immunity as a consequence of restoring lung function after infection.
Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Bone Marrow Cells / pathology
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Emphysema / etiology
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Emphysema / immunology*
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Emphysema / parasitology
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Emphysema / pathology*
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Hookworm Infections / complications
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Hookworm Infections / immunology*
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Hookworm Infections / parasitology
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Hookworm Infections / pathology
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Immunity / immunology*
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Lung / enzymology
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Lung / immunology
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Lung / parasitology
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Lung / pathology
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Lymphocyte Activation / immunology
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Macrophages, Alveolar / parasitology
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Macrophages, Alveolar / pathology
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Matrix Metalloproteinases / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myeloid Cells / immunology*
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Nippostrongylus / immunology*
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Pneumonia / complications
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Pneumonia / immunology
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Pneumonia / parasitology
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Pneumonia / pathology
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Protein Serine-Threonine Kinases / deficiency
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Protein Serine-Threonine Kinases / metabolism
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Pulmonary Fibrosis / complications
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Pulmonary Fibrosis / immunology
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Pulmonary Fibrosis / parasitology
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Pulmonary Fibrosis / pathology
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / deficiency
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Receptors, Transforming Growth Factor beta / metabolism
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T-Lymphocytes / immunology
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Transforming Growth Factor beta / metabolism*
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Wound Healing
Substances
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Receptors, Transforming Growth Factor beta
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Transforming Growth Factor beta
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II
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Matrix Metalloproteinases