CD8+ cells enhance resistance to pulmonary serotype 3 Streptococcus pneumoniae infection in mice.
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.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Sarah E
SE
Weber
Haijun
H
Tian
Liise-anne
LA
Pirofski
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D004195:Disease Models, Animal; D007113:Immunity, Innate; D016130:Immunophenotyping; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology*
D016827:CD8 Antigens; C431698:CD8alpha antigen; C477867:CD8beta antigen