An ahemolytic pneumolysin of streptococcus pneumoniae manipulates human innate and CD4+ T-cell responses and reduces resistance to colonization in mice in a serotype-independent manner

M. Nadeem Khan, John Robert Coleman, Joshua Vernatter, Avanish Kumar Varshney, Chad Dufaud, Liise-anne Pirofski

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background.Some Streptococcus pneumoniae serotypes express an ahemolytic pneumolysin (PLYa). Serotypes that commonly express PLYa, including serotype 8 (ST8) and ST1, are often associated with a low prevalence during colonization but a higher propensity to cause invasive disease. We sought to study the host response to ST8 PLYa in a homologous and heterologous capsular background.

Methods.We genetically exchanged the PLYa of ST8 strain 6308 with the hemolytic PLY (PLYh) of ST3 A66.1 and vice versa and determined the impact of the exchange on nasopharyngeal colonization in mice. Then, to compare the response of human cells to PLYa-expressing and PLYh-expressing strains, we infected human peripheral blood mononuclear cells (PBMCs) with PLY-switched strains and assessed dendritic cell and CD4+ T-cell responses by intracellular cytokine staining. Result.Mice colonized with PLYa-expressing strains had significantly higher colonization densities than those colonized with PLYh-expressing strains, irrespective of capsular background. Compared with infection of PBMCs with PLYh-expressing strains, infection with PLYa-expressing strains induced diminished innate (dendritic cell cytokines, costimulatory receptor, and apoptotic) and adaptive (CD4+ T-cell proliferative and memory interleukin 17A) responses. Conclusion.Our findings demonstrate that PLYa has the potential to manipulate host immunity irrespective of capsule type. PLY exchange between STs expressing PLYa and PLYh could lead to unexpected colonization or invasion phenotypes.

Original languageEnglish (US)
Pages (from-to)1658-1669
Number of pages12
JournalJournal of Infectious Diseases
Volume210
Issue number10
DOIs
StatePublished - Nov 15 2014

Fingerprint

Streptococcus pneumoniae
T-Lymphocytes
Dendritic Cells
Blood Cells
Cytokine Receptors
Interleukin-17
Infection
Capsules
Immunity
Serogroup
Streptococcus pneumoniae plY protein
Staining and Labeling
Cytokines
Phenotype

Keywords

  • apoptosis
  • colonization
  • dendritic cell
  • invasion
  • mice
  • pneumolysin
  • serotype
  • Streptococcus pneumoniae
  • T cell.

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Medicine(all)

Cite this

An ahemolytic pneumolysin of streptococcus pneumoniae manipulates human innate and CD4+ T-cell responses and reduces resistance to colonization in mice in a serotype-independent manner. / Nadeem Khan, M.; Coleman, John Robert; Vernatter, Joshua; Varshney, Avanish Kumar; Dufaud, Chad; Pirofski, Liise-anne.

In: Journal of Infectious Diseases, Vol. 210, No. 10, 15.11.2014, p. 1658-1669.

Research output: Contribution to journalArticle

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abstract = "Background.Some Streptococcus pneumoniae serotypes express an ahemolytic pneumolysin (PLYa). Serotypes that commonly express PLYa, including serotype 8 (ST8) and ST1, are often associated with a low prevalence during colonization but a higher propensity to cause invasive disease. We sought to study the host response to ST8 PLYa in a homologous and heterologous capsular background.Methods.We genetically exchanged the PLYa of ST8 strain 6308 with the hemolytic PLY (PLYh) of ST3 A66.1 and vice versa and determined the impact of the exchange on nasopharyngeal colonization in mice. Then, to compare the response of human cells to PLYa-expressing and PLYh-expressing strains, we infected human peripheral blood mononuclear cells (PBMCs) with PLY-switched strains and assessed dendritic cell and CD4+ T-cell responses by intracellular cytokine staining. Result.Mice colonized with PLYa-expressing strains had significantly higher colonization densities than those colonized with PLYh-expressing strains, irrespective of capsular background. Compared with infection of PBMCs with PLYh-expressing strains, infection with PLYa-expressing strains induced diminished innate (dendritic cell cytokines, costimulatory receptor, and apoptotic) and adaptive (CD4+ T-cell proliferative and memory interleukin 17A) responses. Conclusion.Our findings demonstrate that PLYa has the potential to manipulate host immunity irrespective of capsule type. PLY exchange between STs expressing PLYa and PLYh could lead to unexpected colonization or invasion phenotypes.",
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AU - Vernatter, Joshua

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AU - Dufaud, Chad

AU - Pirofski, Liise-anne

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N2 - Background.Some Streptococcus pneumoniae serotypes express an ahemolytic pneumolysin (PLYa). Serotypes that commonly express PLYa, including serotype 8 (ST8) and ST1, are often associated with a low prevalence during colonization but a higher propensity to cause invasive disease. We sought to study the host response to ST8 PLYa in a homologous and heterologous capsular background.Methods.We genetically exchanged the PLYa of ST8 strain 6308 with the hemolytic PLY (PLYh) of ST3 A66.1 and vice versa and determined the impact of the exchange on nasopharyngeal colonization in mice. Then, to compare the response of human cells to PLYa-expressing and PLYh-expressing strains, we infected human peripheral blood mononuclear cells (PBMCs) with PLY-switched strains and assessed dendritic cell and CD4+ T-cell responses by intracellular cytokine staining. Result.Mice colonized with PLYa-expressing strains had significantly higher colonization densities than those colonized with PLYh-expressing strains, irrespective of capsular background. Compared with infection of PBMCs with PLYh-expressing strains, infection with PLYa-expressing strains induced diminished innate (dendritic cell cytokines, costimulatory receptor, and apoptotic) and adaptive (CD4+ T-cell proliferative and memory interleukin 17A) responses. Conclusion.Our findings demonstrate that PLYa has the potential to manipulate host immunity irrespective of capsule type. PLY exchange between STs expressing PLYa and PLYh could lead to unexpected colonization or invasion phenotypes.

AB - Background.Some Streptococcus pneumoniae serotypes express an ahemolytic pneumolysin (PLYa). Serotypes that commonly express PLYa, including serotype 8 (ST8) and ST1, are often associated with a low prevalence during colonization but a higher propensity to cause invasive disease. We sought to study the host response to ST8 PLYa in a homologous and heterologous capsular background.Methods.We genetically exchanged the PLYa of ST8 strain 6308 with the hemolytic PLY (PLYh) of ST3 A66.1 and vice versa and determined the impact of the exchange on nasopharyngeal colonization in mice. Then, to compare the response of human cells to PLYa-expressing and PLYh-expressing strains, we infected human peripheral blood mononuclear cells (PBMCs) with PLY-switched strains and assessed dendritic cell and CD4+ T-cell responses by intracellular cytokine staining. Result.Mice colonized with PLYa-expressing strains had significantly higher colonization densities than those colonized with PLYh-expressing strains, irrespective of capsular background. Compared with infection of PBMCs with PLYh-expressing strains, infection with PLYa-expressing strains induced diminished innate (dendritic cell cytokines, costimulatory receptor, and apoptotic) and adaptive (CD4+ T-cell proliferative and memory interleukin 17A) responses. Conclusion.Our findings demonstrate that PLYa has the potential to manipulate host immunity irrespective of capsule type. PLY exchange between STs expressing PLYa and PLYh could lead to unexpected colonization or invasion phenotypes.

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