title: Human monocytes promote Th1 and Th17 responses to Streptococcus pneumoniae.
abstract: Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children. Human immunity to pneumococcal infections has been assumed to depend on anticapsular antibodies. However, recent findings from murine models suggest that alternative mechanisms, dependent on T helper cells, are also involved. Although the immunological events in which T helper cells contribute to acquired immunity have been studied in mice, little is known about how these responses are generated in humans. Therefore, we examined bacterial and host factors involved in the induction of Th1 and Th17 responses, using a coculture model of human monocytes and CD4(+) T cells. We show that monocytes promote effector cytokine production by memory T helper cells, leading to a mixed Th1/Th17 (gamma interferon [IFN-γ]/interleukin-17 [IL-17]) profile. Both T helper cytokines were triggered by purified pneumococcal peptidoglycan; however, the balance between the two immune effector arms depended on bacterial viability. Accordingly, live pneumococci triggered a Th1-biased response via monocyte production of IL-12p40, whereas heat-killed pneumococci triggered a Th17 response through TLR2 signaling. An increased understanding of human T helper responses is essential for the development of novel pneumococcal vaccines designed to elicit cell-mediated immunity.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Olliver
authors.forename: Jeffni
authors.initials: J
authors.lastname: Hiew
authors.forename: Peter
authors.initials: P
authors.lastname: Mellroth
authors.forename: Birgitta
authors.initials: B
authors.lastname: Henriques-Normark
authors.forename: Peter
authors.initials: P
authors.lastname: Bergman
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development* / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D010457:Peptidoglycan; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2