Induction of Phagocyte‐Stimulating and Th1‐Promoting Cytokines by In Vitro Stimulation of Human Peripheral Blood Mononuclear Cells with Streptococcus pneumoniae

Abstract

Polymorphonuclear granulocytes, which provide a major defence against Streptococcus pneumoniae infections, are attracted to and activated by various cytokines. The aim of this study was to analyse the cytokine response of human peripheral blood mononuclear cells to stimulation with S. pneumoniae. Strains belonging to serogroups 4, 6, 14, 19 or 23, were isolated from nasopharynx, middle ear fluid, cerebrospinal fluid or blood. All strains induced a marked proliferative response of the peripheral blood mononuclear cells; the stimulatory index was 34+/-11. High levels of pro-inflammatory cytokines were induced, i.e. interleukin (IL)-1beta (53+/-25 ng/ml), IL-6 (347+/-41 ng/ml) and tumour necrosis factor (TNF)-alpha (15+/-4 ng/ml). Also, chemokines and immunoregulatory cytokines including IL-8 (215+/-224 ng/ml), IL-10 (122+/-60 pg/ml), IL-12 (1195+/-648 pg/ml), interferon (IFN)-gamma (18+/-4 ng/ml) and granulocyte macrophage colony-stimulating factor (135+/-80 pg/ml) were induced. Several of these cytokines can up-regulate phagocytosis and the killing of bacteria. Interestingly, strains isolated from middle ear fluid and blood elicited significantly fewer IL-8 and significantly more IL-12 and IL-10 than strains from nasopharynx. They also induced a stronger proliferative response. Our results indicate that pneumococci are potent inducers of cytokines, especially IL-12, favouring T-helper cell type 1 (Th1) responses.

Modulation of the Lung Inflammatory Response to Serotype 8 Pneumococcal Infection by a Human Immunoglobulin M Monoclonal Antibody to Serotype 8 Capsular Polysaccharide

“…There is increasing evidence that cellular immune mechanisms induce resistance to pneumococcal disease and promote pneumococcal clearance (15,20,30,39) through a TH1-type cellular response (3,33). We found that the levels of expression of IL-12 and IFN-␥ were similar in controls and D11-treated mice 6 h after infection.…”

Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide

“…D11 and NAD both reduced PMN IL-8 secretion compared to their respective controls. Different serotypes of live and killed pneumococci have been shown to stimulate IL-8 release from human cells in vitro to varying degrees (1,2,17,25). To our knowledge, it has not been reported previously that type 8 pneumococci can trigger IL-8 release or that IL-8 release can be regulated by type-specific antibodies to pneumococci.…”

Immunization with a ZmpB-Based Protein Vaccine Could Protect against Pneumococcal Diseases in Mice

“…Previous studies have suggested that the Th1 immune response was critical in overcoming pneumococcal infection (1,21,23), while IL-17A regulates acquired immunity to pneumococcal colonization, and it could enhance pneumococcal killing by human neutrophils. In addition, IL-17A plays an important role in suppressing pneumococcal nasal carriage in mice vaccinated mucosally (26,27).…”