title: gp130 on macrophages/granulocytes modulates inflammation during experimental tuberculosis.
abstract: gp130 is a common receptor chain for cytokines such as interleukin (IL)-27 and IL-6. During experimental tuberculosis (TB), IL-27 prevents optimal antimycobacterial protection and limits the pathological sequelae of chronic inflammation. The anti-inflammatory properties of IL-27 have been attributed mainly to its suppressive effect on T helper (TH) cells. However, because gp130 cytokines also suppress the inflammatory immune response of macrophages, IL-27 may also regulate inflammation by limiting the secretion of pro-inflammatory cytokines. To specifically address the role of gp130 cytokines on macrophages, the outcome of experimental TB was analysed in macrophage/neutrophil-specific gp130-deficient (LysM(cre) gp130(loxP/loxP)) mice. In these mice, the enhanced induction of inflammatory cytokines and increased expression of the inducible nitric oxide synthase (NOS2) and LRG47 was linked to a greatly augmented TH17 immune response and matrix metalloproteinase (MMP)-9 expression. However, this amplified inflammatory immune response in Mtb-infected LysM(cre) gp130(loxP/loxP) mice was not associated with reduced bacterial loads and/or accelerated pathology. Our study revealed an immunoregulatory function of gp130 cytokines on macrophages/granulocytes, which is, however, not critical for modulating the outcome of TB.
authors.affiliation: Infection Immunology, Research Center Borstel, Borstel, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Sodenkamp
authors.forename: Jochen
authors.initials: J
authors.lastname: Behrends
authors.forename: Irmgard
authors.initials: I
authors.lastname: Förster
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehlers
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
mesh_terms: D000818:Animals; D050822:Cytokine Receptor gp130 / Q000276:immunology*; D004195:Disease Models, Animal; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D050822:Cytokine Receptor gp130