title: Cytokine-chemokine networks in experimental mycobacterial and schistosomal pulmonary granuloma formation.
abstract: Type-1 and type-2 lung granulomas, respectively, elicited by bead immobilized Mycobacteria bovis and Schistosoma mansoni egg antigens (Ags) display different patterns of chemokine expression. This study tested the hypothesis that chemokine expression patterns were related to upstream cytokine signaling. Using quantitative transcript analysis, we defined expression profiles for 16 chemokines and then examined the in vivo effects of neutralizing antibodies against interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, IL-12, and IL-13. Transcripts for CXCL2, -5, -9, -10, and -11 and the CCL chemokine, CCL3, and lymphotactin (XCL1), were largely enhanced by Th1-related cytokines, IFN-gamma or IL-12. Transcripts for CCL11, CCL22, CCL17, and CCL1 were enhanced largely by Th2-related cytokines, IL-4, IL-10, or IL-13. Transcripts for CCL4, CCL2, CCL8, CCL7, and CCL12 were potentially induced by either Th1- or Th2-related cytokines, although some of these showed biased expression. IFN-gamma and IL-4 enhanced the greatest complement of transcripts, and their neutralization had the greatest anti-inflammatory effect on type-1 and type-2 granulomas, respectively. Th1/Th2 cross-regulation was evident because endogenous Th2 cytokines inhibited type-1, whereas Th1 cytokines inhibited type-2 biased chemokines. These findings reveal a complex cytokine-chemokine regulatory network that dictates profiles of local chemokine expression during T cell-mediated granuloma formation.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Bo-Chin
authors.initials: BC
authors.lastname: Chiu
authors.forename: Christine M
authors.initials: CM
authors.lastname: Freeman
authors.forename: Valerie R
authors.initials: VR
authors.lastname: Stolberg
authors.forename: Eric
authors.initials: E
authors.lastname: Komuniecki
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Lincoln
authors.forename: Steven L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Chensue
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000009:adverse effects; D000947:Antigens, Helminth / Q000009:adverse effects; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006099:Granuloma / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D009163:Mycobacterium bovis / Q000472:pathogenicity; D012550:Schistosoma mansoni / Q000472:pathogenicity; D012555:Schistosomiasis mansoni / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014158:Transcription, Genetic; D014376:Tuberculosis / Q000378:metabolism* / Q000473:pathology
chemical_list: D000906:Antibodies; D000942:Antigens, Bacterial; D000947:Antigens, Helminth; D018925:Chemokines; D016207:Cytokines; D007378:Interleukins; D007371:Interferon-gamma