A Paradox in Bacterial Pathogenesis : activation of the Local Macrophage Inflammasome Is Required for Virulence of Streptococcus uberis
Articolo
Data di Pubblicazione:
2020
Citazione:
A Paradox in Bacterial Pathogenesis : activation of the Local Macrophage Inflammasome Is Required for Virulence of Streptococcus uberis / N. Archer, S.A. Egan, T.J. Coffey, R.D. Emes, M.F. Addis, P.N. Ward, A.M. Blanchard, J.A. Leigh. - In: PATHOGENS. - ISSN 2076-0817. - 9:12(2020 Nov 28), pp. 997.1-997.23. [10.3390/pathogens9120997]
Abstract:
Streptococcus uberis is a common cause of intramammary infection and mastitis in dairy cattle. Unlike other mammary pathogens, S. uberis evades detection by mammary epithelial cells, and the host-pathogen interactions during early colonisation are poorly understood. Intramammary challenge of dairy cows with S. uberis (strain 0140 J) or isogenic mutants lacking the surface-anchored serine protease, SUB1154, demonstrated that virulence was dependent on the presence and correct location of this protein. Unlike the wild-type strain, the mutant lacking SUB1154 failed to elicit IL-1β from ex vivo CD14+ cells obtained from milk (bovine mammary macrophages, BMM), but this response was reinstated by complementation with recombinant SUB1154; the protein in isolation elicited no response. Production of IL-1β was ablated in the presence of various inhibitors, indicating dependency on internalisation and activation of NLRP3 and caspase-1, consistent with inflammasome activation. Similar transcriptomic changes were detected in ex vivo BMM in response to the wild-type or the SUB1154 deletion mutant, consistent with S. uberis priming BMM, enabling the SUB1154 protein to activate inflammasome maturation in a transcriptionally independent manner. These data can be reconciled in a novel model of pathogenesis in which, paradoxically, early colonisation is dependent on the innate response to the initial infection.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
NLRP3; Streptococcus uberis; inflammasome; macrophage; mastitis; pathogenesis
Elenco autori:
N. Archer, S.A. Egan, T.J. Coffey, R.D. Emes, M.F. Addis, P.N. Ward, A.M. Blanchard, J.A. Leigh
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