Cutting Edge: The Immunostimulatory Activity of the Lung Surfactant Protein-A Involves Toll-Like Receptor 4

Guillot, Loïc; Balloy, Viviane; McCormack, Francis X.; Golenbock, Douglas T.; Chignard, Michel; Si‐Tahar, Mustapha

doi:10.4049/jimmunol.168.12.5989

Cited by 289 publications

(177 citation statements)

References 32 publications

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“…Recent evidence indicates that these innate immune moieties have complex interaction patterns and synergism. For instance, SP-A's proinflammatory effect is modulated in part, through TLR4 activation and TLR4 activation can lead to upregulation of cytokine and beta-defensin expression [34,35]. Furthermore, some beta-defensins when co-expressed with other beta-defensins can have synergistic antimicrobial efficacy [36].…”

Section: Discussionmentioning

confidence: 99%

Expression of select immune genes (surfactant proteins A and D, sheep beta defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb

Meyerholz

Kawashima

Gallup

et al. 2006

Developmental & Comparative Immunology

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Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep beta defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p<0.05) from late gestation to term birth. In addition, gene expression of LCM-retrieved type II pneumocytes (CD208+), adjacent epithelium (CD208−) and bronchial epithelium demonstrated that bronchiole-alveolar junction epithelium (combined CD208+/−) had significant (p<0.05) developmental increases in SP-AD, SBD1 and TLR4 mRNA, whereas CD208+ cells had statistically significant increases only with SP-A mRNA. Using immunofluorescence, SP-AD antigen distribution and intensity were also greater with developmental age. These studies show reduced SBD1, SP-AD, and TLR4 expression in the preterm lung and this may underlie enhanced RSV susceptibility. AbstractPreterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep beta defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p<0.05) from late gestation to term birth. In addition, gene expression of LCM-retrieved type II pneumocytes (CD208+), adjacent epithelium (CD208−) and bronchial epithelium demonstrated that bronchiole-alveolar junction epithelium (combined CD208+/−) had significant (p<0.05) developmental increases in SP-AD, SBD1 and TLR4 mRNA, whereas CD208+ cells had statistically significant increases only with SP-A mRNA. Using immunofluorescence, SP-AD antigen distribution and intensity were also greater with developmental age. These studies show reduced SBD1, SP-AD, and TLR4 expression in the preterm lung and this may underlie enhanced RSV susceptibility.

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Section: Discussionmentioning

confidence: 99%

Expression of select immune genes (surfactant proteins A and D, sheep beta defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb

Meyerholz

Kawashima

Gallup

et al. 2006

Developmental & Comparative Immunology

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“…The general issue is the purity of the ligands. For TLR-4, a number of host factors (HSP60, HSP70, Surfactant Protein-A) have been described that could activate the signaling cascade (17)(18)(19). However, it is technically very difficult to prove that this effect is not because of some minute contamination with LPS, as this is such a powerful ligand for TLR-4.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

How epithelial cells detect danger: aiding the immune response

Vroling

Fokkens

Drunen

2008

Allergy

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The epithelial layer occupies a strategic important location between an organisms’ interior and exterior environment. Although as such it forms a physical barrier between both environments, it became clear that the role of the epithelium extends far beyond this rather passive role. Through specialized receptors and other more general mechanisms, the epithelial layer is not only able to sense changes in its environment but also to actively respond to these changes. These responses allow the epithelium to contribute to wound and tissue repair, to the defense against micro‐organisms, and to the control and regulation of the locale immune response. In this review, we focus on signals acting on epithelium from the exterior environment, how these signals are processed and identify research challenges.

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“…Interestingly, SP-A was recently also shown to bind to TLR4 [69]. Furthermore, heatshock proteins can signal towards phagocytic cells via CD91 and via scavenger receptor-A [45,46].…”

Section: Opsonization May Direct the Cellular Response To Apoptotic Cmentioning

confidence: 99%

Mini‐review: A pivotal role for innate immunity in the clearance of apoptotic cells

et al. 2004

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Apoptotic cells can be recognized and taken up by both macrophages and dendritic cells. Phagocytosis of apoptotic cells generally leads to active suppression of cytokine production by professional phagocytes. This is different from the response towards cells that die by necrosis, which induce a pro-inflammatory cytokine profile. Uptake of apoptotic cells involves a large number of receptors and opsonins, which bind to cellular ligands exposed during the various stages of apoptotic cell death. Among the opsonins of apoptotic cells, complement factors, including C1q, and complement-activating members of the pentraxin family play an important role. This is indicated by in vitro phagocytosis studies and supported by the susceptibility to systemic autoimmunity of carriers of genetic deficiencies for early complement proteins. The present review summarizes the role of molecules of innate immunity in the handling of apoptotic cells by macrophages and dendritic cells. It is proposed that C1q and other opsonins prevent autoimmunity and maintain self-tolerance by supporting the efficient clearance of apoptotic material, as well as by actively modulating phagocyte function.

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Cutting Edge: The Immunostimulatory Activity of the Lung Surfactant Protein-A Involves Toll-Like Receptor 4

Cited by 289 publications

References 32 publications

Expression of select immune genes (surfactant proteins A and D, sheep beta defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb

Expression of select immune genes (surfactant proteins A and D, sheep beta defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb

How epithelial cells detect danger: aiding the immune response

Mini‐review: A pivotal role for innate immunity in the clearance of apoptotic cells

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