title: Pattern recognition receptor-mediated cytokine response in infants across 4 continents.
abstract: BACKGROUND
  Susceptibility to infection as well as response to vaccination varies among populations. To date, the underlying mechanisms responsible for these clinical observations have not been fully delineated. Because innate immunity instructs adaptive immunity, we hypothesized that differences between populations in innate immune responses may represent a mechanistic link to variation in susceptibility to infection or response to vaccination.
  
  
  OBJECTIVE
  Determine whether differences in innate immune responses exist among infants from different continents of the world.
  
  
  METHODS
  We determined the innate cytokine response following pattern recognition receptor (PRR) stimulation of whole blood from 2-year-old infants across 4 continents (Africa, North America, South America, and Europe).
  
  
  RESULTS
  We found that despite the many possible genetic and environmental exposure differences in infants across 4 continents, innate cytokine responses were similar for infants from North America, South America, and Europe. However, cells from South African infants secreted significantly lower levels of cytokines than did cells from infants from the 3 other sites, and did so following stimulation of extracellular and endosomal but not cytosolic PRRs.
  
  
  CONCLUSIONS
  Substantial differences in innate cytokine responses to PRR stimulation exist among different populations of infants that could not have been predicted. Delineating the underlying mechanism(s) for these differences will not only aid in improving vaccine-mediated protection but possibly also provide clues for the susceptibility to infection in different regions of the world.
authors.affiliation: Department of Experimental Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kinga K
authors.initials: KK
authors.lastname: Smolen
authors.affiliation: Department of Experimental Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Candice E
authors.initials: CE
authors.lastname: Ruck
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Edgardo S
authors.initials: ES
authors.lastname: Fortuno
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ho
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Pedro
authors.initials: P
authors.lastname: Dimitriu
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: William W
authors.initials: WW
authors.lastname: Mohn
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: David P
authors.initials: DP
authors.lastname: Speert
authors.affiliation: Centro de Investigaciones FEPIS, Esmeraldas, Quininde, Ecuador; Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom; Centro de Investgación en Enfermedades Infecciosas, Escuela de Biología, Pontificia Universidad Católica del Ecuador, Casilla, Quito, Ecuador.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Cooper
authors.affiliation: Immunology Unit, Division of Medical Microbiology, Department of Pathology, NHLS and Stellenbosch University, Matieland, South Africa.
authors.forename: Monika
authors.initials: M
authors.lastname: Esser
authors.affiliation: Department of Paediatrics, Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium.
authors.forename: Tessa
authors.initials: T
authors.lastname: Goetghebuer
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchant
authors.affiliation: Department of Experimental Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: tkollm@mac.com.
authors.forename: Tobias R
authors.initials: TR
authors.lastname: Kollmann
mesh_terms: D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis*; D004198:Disease Susceptibility; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007226:Infant Mortality; D007239:Infections / Q000276:immunology / Q000401:mortality; D051192:Receptors, Pattern Recognition / Q000502:physiology*; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D016207:Cytokines; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors
keywords: Innate immunity; global; immune development; infectious disease