title: Low induction of proinflammatory cytokines parallels evolutionary success of modern strains within the Mycobacterium tuberculosis Beijing genotype.
abstract: One of the most widespread clades of Mycobacterium tuberculosis worldwide, the Beijing genotype family, consists of ancient (atypical) and modern (typical) strains. Modern Beijing strains outcompete ancient strains in terms of prevalence, while reserving a higher degree of genetic conservation. We hypothesize that their selective advantage lies in eliciting a different host immune response. Bead-disrupted lysates of a collection of different M. tuberculosis strains of the modern (n = 7) or ancient (n = 7) Beijing genotype, as well as the Euro-American lineage (n = 6), were used for induction of ex vivo cytokine production in peripheral blood mononuclear cells (PBMCs) from 10 healthy individuals. Hierarchical clustering and multivariate regression analyses were used to study possible differences in production of nine cytokines. Modern and ancient M. tuberculosis Beijing genotypes induced different cytokine signatures. Overall induction of interleukin-1β (IL-1β), gamma interferon (IFN-γ), and IL-22 was 38 to 40% lower after stimulation with modern Beijing strains (corrected P values of <0.0001, 0.0288, and 0.0002, respectively). Euro-American reactivation strains induced 2-fold more TNF-α production than both types of Beijing strains. The observed differences in cytokine induction point to a reduction in proinflammatory cytokine response as a possible contributing factor to the evolutionary success of modern Beijing strains.
authors.affiliation: Department of Medicine and Nijmegen Institute for Infection, Inflammation, and Immunity (N4i), Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: van Laarhoven
authors.forename: Jornt J
authors.initials: JJ
authors.lastname: Mandemakers
authors.forename: Johanneke
authors.initials: J
authors.lastname: Kleinnijenhuis
authors.forename: Mimount
authors.initials: M
authors.lastname: Enaimi
authors.forename: Ekta
authors.initials: E
authors.lastname: Lachmandas
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Dick
authors.initials: D
authors.lastname: van Soolingen
authors.forename: Reinout
authors.initials: R
authors.lastname: van Crevel
mesh_terms: D000995:Antitubercular Agents; D005075:Biological Evolution; D002681:China / Q000453:epidemiology; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D016207:Cytokines
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