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Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent

Koen Breyne (UGent) , Steven Cool (UGent) , Dieter Demon (UGent) , Kristel Demeyere (UGent) , Tom Vandenberghe (UGent) , Peter Vandenabeele (UGent) , Harald Carlsen, Wim Van Den Broeck (UGent) , Niek Sanders (UGent) and Evelyne Meyer (UGent)
(2014) PLOS ONE. 9(8).
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Abstract
Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1.
Keywords
AUREUS-INDUCED MASTITIS, STAPHYLOCOCCUS-AUREUS, INNATE IMMUNE-RESPONSES, NF-KAPPA-B, ESCHERICHIA-COLI, EPITHELIAL-CELLS, MURINE MODEL, MATRIX METALLOPROTEINASES, ALVEOLAR MACROPHAGES, BOVINE NEUTROPHILS

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Citation

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Chicago
Breyne, Koen, Steven Cool, Dieter Demon, Kristel Demeyere, Tom Vandenberghe, Peter Vandenabeele, Harald Carlsen, Wim Van Den Broeck, Niek Sanders, and Evelyne Meyer. 2014. “Non-classical ProIL-1beta Activation During Mammary Gland Infection Is Pathogen-dependent but Caspase-1 Independent.” Plos One 9 (8).
APA
Breyne, K., Cool, S., Demon, D., Demeyere, K., Vandenberghe, T., Vandenabeele, P., Carlsen, H., et al. (2014). Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent. PLOS ONE, 9(8).
Vancouver
1.
Breyne K, Cool S, Demon D, Demeyere K, Vandenberghe T, Vandenabeele P, et al. Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent. PLOS ONE. 2014;9(8).
MLA
Breyne, Koen, Steven Cool, Dieter Demon, et al. “Non-classical ProIL-1beta Activation During Mammary Gland Infection Is Pathogen-dependent but Caspase-1 Independent.” PLOS ONE 9.8 (2014): n. pag. Print.
@article{5785011,
  abstract     = {Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1.},
  articleno    = {e105680},
  author       = {Breyne, Koen and Cool, Steven and Demon, Dieter and Demeyere, Kristel and Vandenberghe, Tom and Vandenabeele, Peter and Carlsen, Harald and Van Den Broeck, Wim and Sanders, Niek and Meyer, Evelyne},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {AUREUS-INDUCED MASTITIS,STAPHYLOCOCCUS-AUREUS,INNATE IMMUNE-RESPONSES,NF-KAPPA-B,ESCHERICHIA-COLI,EPITHELIAL-CELLS,MURINE MODEL,MATRIX METALLOPROTEINASES,ALVEOLAR MACROPHAGES,BOVINE NEUTROPHILS},
  language     = {eng},
  number       = {8},
  pages        = {12},
  title        = {Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent},
  url          = {http://dx.doi.org/10.1371/journal.pone.0105680},
  volume       = {9},
  year         = {2014},
}

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