title: Rapid interferon-gamma release from natural killer cells induced by a streptococcal commensal.
abstract: Interferon-gamma (IFN-γ) is a critical cytokine for the initiation of immune responses against a variety of infectious agents and malignancies. We found that a range of Gram-positive and Gram-negative bacteria stimulated the rapid release (<24 h) of IFN-γ from murine leukocytes. Using fluorescence activated cell sorting and cd1d(-/-) and rag1(-/-) mice, we determined that dendritic cells (DCs) and natural killer (NK) cells were primarily responsible for IFN-γ release by Streptococcus salivarius, a Gram-positive commensal, previously noted to possess potent interleukin-12 (IL-12)-inducing potential. IFN-γ release from NK cells required DC:NK membrane contact and IL-12/IL-18 expression, but was independent of lymphocyte function-associated antigen-1-mediated interactions. IFN-γ release in response to bacteria was maintained in mice deficient for Toll-like receptor (TLR)-2 and TLR-4, suggesting that bacteria activate antigen-presenting cells via multiple, redundant pathways. Together, our results suggest that Gram-positive bacteria may be useful in driving NK cell activation and T helper 1 polarization and have the potential for development as effective adjuvants.
authors: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors: Anthea L
authors: AL
authors: Bouwer
authors: Sarah C
authors: SC
authors: Saunderson
authors: Amy C
authors: AC
authors: Dunn
authors: Katherine L
authors: KL
authors: Lester
authors: Lynsey R
authors: LR
authors: Crowley
authors: Ralph W
authors: RW
authors: Jack
authors: Alexander D
authors: AD
authors: McLellan
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D005434:Flow Cytometry; D006090:Gram-Negative Bacteria / Q000145:classification / Q000276:immunology / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000145:classification / Q000276:immunology / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013291:Streptococcus / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; D018398:Homeodomain Proteins; D020382:Interleukin-18; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C064658:RAG-1 protein; D018664:Interleukin-12; D007371:Interferon-gamma