title: Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection.
abstract: Resistance to Mycobacterium tuberculosis requires the host to restrict bacterial replication while preventing an over-exuberant inflammatory response. Interferon (IFN) γ is crucial for activating macrophages and also regulates tissue inflammation. We dissociate these two functions and show that IFN-γ(-/-) memory CD4(+) T cells retain their antimicrobial activity but are unable to suppress inflammation. IFN-γ inhibits CD4(+) T cell production of IL-17, which regulates neutrophil recruitment. In addition, IFN-γ directly inhibits pathogenic neutrophil accumulation in the infected lung and impairs neutrophil survival. Regulation of neutrophils is important because their accumulation is detrimental to the host. We suggest that neutrophilia during tuberculosis indicates failed Th1 immunity or loss of IFN-γ responsiveness. These results establish an important antiinflammatory role for IFN-γ in host protection against tuberculosis.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bisweswar
authors.initials: B
authors.lastname: Nandi
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Behar
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D009504:Neutrophils / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011828:Radiation Chimera; D015398:Signal Transduction / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D020381:Interleukin-17; C499308:Rag2 protein, mouse; D007371:Interferon-gamma