Neonatal Skin in Mice and Humans Expresses Increased Levels of Antimicrobial Peptides: Innate Immunity During Development of the Adaptive Response

Dorschner, Robert A.; Lin, Kenneth H.; Murakami, Masamoto; Gallo, Richard L.

doi:10.1203/01.pdr.0000057205.64451.b7

Cited by 133 publications

(106 citation statements)

References 34 publications

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“…Furthermore, expression of the cathelicidin gene ( CRAMP -shown to be 10-100 fold greater in neonatal mice than in the adult), is thought to provide an important compensatory neonatal innate immune defence mechanism [15] .…”

Section: B-defensinsmentioning

confidence: 99%

Differential antimicrobial peptide gene expression patterns during early chicken embryological development

Meade

Higgs

Lloyd

et al. 2009

Developmental & Comparative Immunology

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Section: B-defensinsmentioning

confidence: 99%

Differential antimicrobial peptide gene expression patterns during early chicken embryological development

Meade

Higgs

Lloyd

et al. 2009

Developmental & Comparative Immunology

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“…Over 26 human beta-defensins have been identified [11,12]. Expression of some beta-defensins, such as human beta-defensin-1 (HBD-1), is constitutive, whereas expression of other beta-defensins, such as HBD-2, 3, and 4, [4,8,13], mouse beta-defensin-2 [14], tracheal antimicrobial peptide (TAP) and lingual antimicrobial peptide (LAP) of cattle, is inducible [15 -18]. Induction often occurs secondary to activation of Toll-like receptor 4 (TLR 4) and NF-kappa B signaling [4,5].…”

Section: Introductionmentioning

confidence: 99%

Differential expression of sheep beta-defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia

Ackermann¹,

Gallup²,

Zabner³

et al. 2004

Microbial Pathogenesis

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Beta-defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some beta-defensins is increased by bacterial-induced inflammatory responses whereas expression of other beta-defensins is constitutive. Two beta-defensins are expressed in lungs of sheep (sheep beta-defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica, a Gram-negative bacteria known to induce expression of bovine beta-defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10 9 ). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Coinoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, but not in leukocytes. This study suggests that SDB-1 expression occurs in epithelia and decreases during severe bacterial pneumonia, which is in contrast to the increase that occurs with PI-3 infection. RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. AuthorsMark R. Ackermann, Jack M. Abstract Beta-defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some beta-defensins is increased by bacterial-induced inflammatory responses whereas expression of other beta-defensins is constitutive. Two beta-defensins are expressed in lungs of sheep (sheep beta-defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica, a Gram-negative bacteria known to induce expression of bovine beta-defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10 9 ). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Co-inoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, b...

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“…This was not unexpected and is most likely explained by the fact that in the host, antimicrobial mechanisms are thought to act synergistically to kill bacteria. Synergistic bactericidal activity has been demonstrated experimentally in vitro between AMPs, and between AMPs and other innate immunity proteins such as lysozyme, which is one of the most abundant antimicrobial proteins in the airspaces of the lung (53)(54)(55)(56). Future studies will characterize the sensitivity of the GBS ponA mutant to other host bactericidal factors that are present in the airway.…”

Section: Discussionmentioning

confidence: 97%

A Streptococcal Penicillin-Binding Protein Is Critical for Resisting Innate Airway Defenses in the Neonatal Lung

Jones¹,

Mertz

Carl³

et al. 2007

The Journal of Immunology

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Group B streptococcus (GBS) is a major cause of neonatal pneumonia. The early interactions between innate airway defenses and this pathogen are likely to be a critical factor in determining the outcome for the host. The surface-localized penicillin-binding protein (PBP)1a, encoded by ponA, is known to be an important virulence trait in a sepsis model of GBS infection that promotes resistance to neutrophil killing and more specifically to neutrophil antimicrobial peptides (AMPs). In this study, we used an aerosolization model to explore the role of PBP1a in evasion of innate immune defenses in the neonatal lung. The ponA mutant strain was cleared more rapidly from the lungs of neonatal rat pups compared with the wild-type strain, which could be linked to a survival defect in the presence of alveolar macrophages (AM). Rat AM were found to secrete β-defensin and cathelicidin AMP homologues, and the GBS ponA mutant was more susceptible than the wild-type strain to killing by these peptides in vitro. Collectively, our observations suggest that PBP1a-mediated resistance to AM AMPs promotes the survival of GBS in the neonatal lung. Additionally, AM are traditionally thought to clear bacteria through phagocytic uptake; our data indicate that secretion of AMPs may also participate in limiting bacterial replication in the airway.

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Neonatal Skin in Mice and Humans Expresses Increased Levels of Antimicrobial Peptides: Innate Immunity During Development of the Adaptive Response

Cited by 133 publications

References 34 publications

Differential antimicrobial peptide gene expression patterns during early chicken embryological development

Differential antimicrobial peptide gene expression patterns during early chicken embryological development

Differential expression of sheep beta-defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia

A Streptococcal Penicillin-Binding Protein Is Critical for Resisting Innate Airway Defenses in the Neonatal Lung

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