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TLR-mediated inflammatory responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial lipoproteins.


ABSTRACT: Streptococcus pneumoniae infections induce inflammatory responses that contribute toward both disease pathogenesis and immunity, but the host-pathogen interactions that mediate these effects are poorly defined. We used the surface lipoprotein-deficient ?lgt pneumococcal mutant strain to test the hypothesis that lipoproteins are key determinants of TLR-mediated immune responses to S. pneumoniae. We show using reporter assays that TLR2 signaling is dependent on pneumococcal lipoproteins, and that macrophage NF-?B activation and TNF-? release were reduced in response to the ?lgt strain. Differences in TNF-? responses between ?lgt and wild-type bacteria were abrogated for macrophages from TLR2- but not TLR4-deficient mice. Transcriptional profiling of human macrophages revealed attenuated TLR2-associated responses to ?lgt S. pneumoniae, comprising many NF-?B-regulated proinflammatory cytokine and chemokine genes. Importantly, non-TLR2-associated responses were preserved. Experiments using leukocytes from IL-1R-associated kinase-4-deficient patients and a mouse pneumonia model confirmed that proinflammatory responses were lipoprotein dependent. Our data suggest that leukocyte responses to bacterial lipoproteins are required for TLR2- and IL-1R-associated kinase-4-mediated inflammatory responses to S. pneumoniae.

SUBMITTER: Tomlinson G 

PROVIDER: S-EPMC4170674 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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TLR-mediated inflammatory responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial lipoproteins.

Tomlinson Gillian G   Chimalapati Suneeta S   Pollard Tracey T   Lapp Thabo T   Cohen Jonathan J   Camberlein Emilie E   Stafford Sian S   Periselneris Jimstan J   Aldridge Christine C   Vollmer Waldemar W   Picard Capucine C   Casanova Jean-Laurent JL   Noursadeghi Mahdad M   Brown Jeremy J  

Journal of immunology (Baltimore, Md. : 1950) 20140829 7


Streptococcus pneumoniae infections induce inflammatory responses that contribute toward both disease pathogenesis and immunity, but the host-pathogen interactions that mediate these effects are poorly defined. We used the surface lipoprotein-deficient ∆lgt pneumococcal mutant strain to test the hypothesis that lipoproteins are key determinants of TLR-mediated immune responses to S. pneumoniae. We show using reporter assays that TLR2 signaling is dependent on pneumococcal lipoproteins, and that  ...[more]

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