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Bacterial lipoproteins and other factors released by Francisella tularensis modulate human neutrophil lifespan: Effects of a TLR1 SNP on apoptosis inhibition.
- Source :
-
Cellular microbiology [Cell Microbiol] 2018 Feb; Vol. 20 (2). Date of Electronic Publication: 2017 Nov 21. - Publication Year :
- 2018
-
Abstract
- Francisella tularensis infects several cell types including neutrophils, and aberrant neutrophil accumulation contributes to tissue destruction during tularaemia. We demonstrated previously that F. tularensis strains Schu S4 and live vaccine strain markedly delay human neutrophil apoptosis and thereby prolong cell lifespan, but the bacterial factors that mediate this aspect of virulence are undefined. Herein, we demonstrate that bacterial conditioned medium (CM) can delay apoptosis in the absence of direct infection. Biochemical analyses show that CM contained F. tularensis surface factors as well as outer membrane components. Our previous studies excluded roles for lipopolysaccharide and capsule in apoptosis inhibition, and current studies of [ <superscript>14</superscript> C] acetate-labelled bacteria argue against a role for other bacterial lipids in this process. At the same time, studies of isogenic mutants indicate that TolC and virulence factors whose expression requires FevR or MglA were also dispensable, demonstrating that apoptosis inhibition does not require Type I or Type VI secretion. Instead, we identified bacterial lipoproteins (BLPs) as active factors in CM. Additional studies of isolated BLPs demonstrated dose-dependent neutrophil apoptosis inhibition via a TLR2-dependent mechanism that is significantly influenced by a common polymorphism, rs5743618, in human TLR1. These data provide fundamental new insight into pathogen manipulation of neutrophil lifespan and BLP function.<br /> (© 2017 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.)
- Subjects :
- Francisella tularensis genetics
Humans
Macrophages metabolism
Macrophages microbiology
Macrophages physiology
Neutrophils metabolism
Neutrophils microbiology
Tularemia metabolism
Tularemia microbiology
Virulence genetics
Virulence Factors metabolism
Apoptosis physiology
Bacterial Proteins metabolism
Francisella tularensis metabolism
Lipoproteins metabolism
Neutrophils physiology
Polymorphism, Single Nucleotide genetics
Toll-Like Receptor 1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1462-5822
- Volume :
- 20
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cellular microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 29063667
- Full Text :
- https://doi.org/10.1111/cmi.12795