Host cell kinases, α5 and β1 integrins, and Rac1 signalling on the microtubule cytoskeleton are important for non-typable Haemophilus influenzae invasion of respiratory epithelial cells.

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dc.contributor.author López-Gómez, Antonio
dc.contributor.author Cano, Victoria
dc.contributor.author Moranta Mesquida, David
dc.contributor.author Morey, Pau
dc.contributor.author García del Portillo, Francisco
dc.contributor.author Bengoechea, José Antonio
dc.contributor.author Garmendia, Junkal
dc.date.accessioned 2018-09-14T11:15:09Z
dc.identifier.uri http://hdl.handle.net/11201/147421
dc.description.abstract [eng] Non-typable Haemophilus influenzae (NTHi) is a common commensal of the human nasopharynx, but causes opportunistic infection when the respiratory tract is compromised by infection or disease. The ability of NTHi to invade epithelial cells has been described, but the underlying molecular mechanisms are poorly characterized. We previously determined that NTHi promotes phosphorylation of the serine-threonine kinase Akt in A549 human lung epithelial cells, and that Akt phosphorylation and NTHi cell invasion are prevented by inhibition of phosphoinositide 3-kinase (PI3K). Because PI3K-Akt signalling is associated with several host cell networks, the purpose of the current study was to identify eukaryotic molecules important for NTHi epithelial invasion. We found that inhibition of Akt activity reduced NTHi internalization; differently, bacterial entry was increased by phospholipase Cc1 inhibition but was not affected by protein kinase inhibition. We also found that a5 and b1 integrins, and the tyrosine kinases focal adhesion kinase and Src, are important for NTHi A549 cell invasion. NTHi internalization was shown to be favoured by activation of Rac1 guanosine triphosphatase (GTPase), together with the guanine nucleotide exchange factor Vav2 and the effector Pak1. Also, Pak1 might be associated with inactivation of the microtubule destabilizing agent Op18/stathmin, to facilitate microtubule polymerization and NTHi entry. Conversely, inhibition of RhoA GTPase and its effector ROCK increased the number of internalized bacteria. Src and Rac1 were found to be important for NTHi-triggered Akt phosphorylation. An increase in host cyclic AMP reduced bacterial entry, which was linked to protein kinase A. These findings suggest that NTHi finely manipulates host signalling molecules to invade respiratory epithelial cells.
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dc.relation.isformatof Versió postprint del document publicat a: https://doi.org/10.1099/mic.0.059972-0
dc.relation.ispartof Microbiology-UK, 2012, vol. 158, num. 9, p. 2384-2398
dc.subject.classification 576 - Biologia cel·lular i subcel·lular. Citologia
dc.subject.other 576 - Cellular and subcellular biology. Cytology
dc.title Host cell kinases, α5 and β1 integrins, and Rac1 signalling on the microtubule cytoskeleton are important for non-typable Haemophilus influenzae invasion of respiratory epithelial cells.
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion
dc.date.updated 2018-09-14T11:15:10Z
dc.date.embargoEndDate info:eu-repo/date/embargoEnd/2075-01-01
dc.embargo 2075-01-01
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess
dc.identifier.doi https://doi.org/10.1099/mic.0.059972-0


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