title: Tuberculosis is associated with a down-modulatory lung immune response that impairs Th1-type immunity.
abstract: Immune mediators associated with human tuberculosis (TB) remain poorly defined. This study quantified levels of lung immune mediator gene expression at the time of diagnosis and during anti-TB treatment using cells obtained by induced sputum. Upon comparison to patients with other infectious lung diseases and volunteers, active pulmonary TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity. Despite the concomitant heightened levels of Th1-type mediators, immune activation may be rendered ineffectual by high levels of intracellular (SOCS and IRAK-M) and extracellular (IL-10 and TGF-betaRII, IL-1Rn, and IDO) immune suppressive mediators. These modulators are a direct response to Mycobacterium tuberculosis as, by day 30 of anti-TB treatment, many suppressive factors declined to that of controls whereas most Th1-type and innate immune mediators rose above pretreatment levels. Challenge of human immune cells with M. tuberculosis in vitro up-regulated these immune modulators as well. The observed low levels of NO synthase-2 produced by alveolar macrophages at TB diagnosis, along with the heightened amounts of suppressive mediators, support the conclusion that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type and innate immunity as an immunopathological strategy. Our data highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response.
authors.affiliation: Institute of Thoracic Diseases, Clementino Fraga Filho University Hospital of Federal University of Rio de Janeiro, Brazil.
authors.forename: Alexandre S
authors.initials: AS
authors.lastname: Almeida
authors.forename: Patrícia M
authors.initials: PM
authors.lastname: Lago
authors.forename: Neio
authors.initials: N
authors.lastname: Boechat
authors.forename: Richard C
authors.initials: RC
authors.lastname: Huard
authors.forename: Luiz C O
authors.initials: LC
authors.lastname: Lazzarini
authors.forename: Adalberto R
authors.initials: AR
authors.lastname: Santos
authors.forename: Marcelo
authors.initials: M
authors.lastname: Nociari
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhu
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Perez-Sweeney
authors.forename: Heejung
authors.initials: H
authors.lastname: Bang
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Ni
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Gibson
authors.forename: Vera C
authors.initials: VC
authors.lastname: Flores
authors.forename: Lorena R
authors.initials: LR
authors.lastname: Pecanha
authors.forename: Afrânio L
authors.initials: AL
authors.lastname: Kritski
authors.forename: José R
authors.initials: JR
authors.lastname: Lapa e Silva
authors.forename: John L
authors.initials: JL
authors.lastname: Ho
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000276:immunology / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators