CD8+ cells enhance resistance to pulmonary serotype 3 Streptococcus pneumoniae infection in mice

Sarah E. Weber, Haijun Tian, Liise-anne Pirofski

Research output: Contribution to journalArticle

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Abstract

Despite the success of the pneumococcal conjugate vaccine, pneumococcal pneumonia remains a significant clinical problem, and there is still much to learn about natural resistance and cellular immunity to pneumococcus. We investigated the role of T lymphocytes in resistance to serotype (ST) 3 Streptococcus pneumoniae in an intranasal infection model in C57BL/6 (wild-type [Wt]) and CD8+ (CD8-/-)- and CD4+ (MHC class II-/-)-deficient mice. CD8-/- mice exhibited significantly more bacterial dissemination and lung inflammation and a significantly more lethal phenotype than Wt mice. However, there was no difference in the bacterial dissemination, lung inflammation, or survival of Wt and MHC class II -/- mice. Perforin (Pfn)-/- and IFN-γ-/- mice, which were used to dissect the role of CD8+ T cells in our model, also exhibited a more lethal survival phenotype than Wt mice. Comparison of lung chemokine/cytokine levels by Luminex and cellular recruitment by FACS in Wt mice and knockout strains revealed that CD8-/- and IFN-γ-/- mice, which had the most lethal survival phenotype, had more CD4+IL-17+ T (Th17) cells, IL-17, neutrophil chemoattractants, and lung neutrophils, and fewer regulatory T cells than Wt mice. CD4+ T cell depletion improved the survival of ST-infected CD8-/- mice, and survival studies in Th17-deficient mice revealed that the Th17 response was dispensable for ST3 resistance in our model. Taken together, these findings demonstrate that CD8+ cells are required, but CD4+ T cells are dispensable for resistance to ST3 pneumonia in mice and suggest a previously unsuspected role for CD8+ cells in modulating the inflammatory response to ST3.

Original languageEnglish (US)
Pages (from-to)432-442
Number of pages11
JournalJournal of Immunology
Volume186
Issue number1
DOIs
StatePublished - Jan 1 2011

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Pneumococcal Infections
Lung
T-Lymphocytes
Pneumonia
Interleukin-17
Streptococcus pneumoniae
Phenotype
Innate Immunity
Neutrophils
Serogroup
Pneumococcal Pneumonia
Th17 Cells
Conjugate Vaccines
Pneumococcal Vaccines
Chemotactic Factors
Regulatory T-Lymphocytes
Chemokines
Knockout Mice
Cellular Immunity
Cytokines

ASJC Scopus subject areas

  • Immunology

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CD8+ cells enhance resistance to pulmonary serotype 3 Streptococcus pneumoniae infection in mice. / Weber, Sarah E.; Tian, Haijun; Pirofski, Liise-anne.

In: Journal of Immunology, Vol. 186, No. 1, 01.01.2011, p. 432-442.

Research output: Contribution to journalArticle

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