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The frustrated host response to Legionella pneumophila is bypassed by MyD88-dependent translation of pro-inflammatory cytokines.

Authors :
Seblewongel Asrat
Aisling S Dugan
Ralph R Isberg
Source :
PLoS Pathogens, Vol 10, Iss 7, p e1004229 (2014)
Publication Year :
2014
Publisher :
Public Library of Science (PLoS), 2014.

Abstract

Many pathogens, particularly those that require their host for survival, have devised mechanisms to subvert the host immune response in order to survive and replicate intracellularly. Legionella pneumophila, the causative agent of Legionnaires' disease, promotes intracellular growth by translocating proteins into its host cytosol through its type IV protein secretion machinery. At least 5 of the bacterial translocated effectors interfere with the function of host cell elongation factors, blocking translation and causing the induction of a unique host cell transcriptional profile. In addition, L. pneumophila also interferes with translation initiation, by preventing cap-dependent translation in host cells. We demonstrate here that protein translation inhibition by L. pneumophila leads to a frustrated host MAP kinase response, where genes involved in the pathway are transcribed but fail to be translated due to the bacterium-induced protein synthesis inhibition. Surprisingly, few pro-inflammatory cytokines, such as IL-1α and IL-1β, bypass this inhibition and get synthesized in the presence of Legionella effectors. We show that the selective synthesis of these genes requires MyD88 signaling and takes place in both infected cells that harbor bacteria and neighboring bystander cells. Our findings offer a perspective of how host cells are able to cope with pathogen-encoded activities that disrupt normal cellular process and initiate a successful inflammatory response.

Details

Language :
English
ISSN :
15537366 and 15537374
Volume :
10
Issue :
7
Database :
Directory of Open Access Journals
Journal :
PLoS Pathogens
Publication Type :
Academic Journal
Accession number :
edsdoj.542bee6f764a4c2f9afd5c7804c277a4
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.ppat.1004229