title: Analysis of Toll-like receptors, iNOS and cytokine profiles in patients with pulmonary tuberculosis during anti-tuberculosis treatment.
abstract: Toll-like receptors (TLRs) play an important role in mycobacterial infection, although little is known about the roles of these receptors, cytokines and nitric oxide during anti-tuberculosis treatment. Our objective was to evaluate the mRNA and cell surface expression of TLR2 and TLR4; inducible nitric oxide synthase (iNOS) expression; and cytokine Th1, Th2 and Th17 profiles in pulmonary tuberculosis patients at different time points of anti-tuberculosis treatment. Peripheral blood mononuclear cells (PBMCs) were obtained from PPD(+) healthy controls and from patients receiving anti-tuberculosis treatment. Gene expression quantification was performed by qPCR, cell surface expression was assessed using flow cytometry, and cytokine quantification was conducted using the CBA technique. The treated patients presented higher gene expression and higher numbers of receptors on the cell surface of lymphocytes and monocytes than did control individuals. IL-12 and IFN-γ levels increased after the start of treatment, whereas TNF-α levels were reduced. TGF-β presented the highest levels during treatment. IL-10 and IL-17 expression and production tended to increase during treatment. iNOS gene expression was reduced throughout treatment in patients. Our results suggest that anti-tuberculosis treatment modulates the immune response, inducing an increase in the expression of TLRs and pro- and anti-inflammatory cytokines to combat bacteria and reduce the inflammatory process.
authors.affiliation: Tropical Diseases Department, Botucatu School of Medicine - UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Larissa Ragozo Cardoso
authors.initials: LR
authors.lastname: de Oliveira
authors.affiliation: Tropical Diseases Department, Botucatu School of Medicine - UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Eliana
authors.initials: E
authors.lastname: Peresi
authors.affiliation: Flow Cytometry Laboratory, Hemocenter, Botucatu School of Medicine - UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Marjorie de Assis
authors.initials: Mde A
authors.lastname: Golim
authors.affiliation: Tropical Diseases Department, Botucatu School of Medicine - UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Gatto
authors.affiliation: Department of Microbiology and Immunology, Biosciences Institute, UNESP, Botucatu São Paulo, Brazil.
authors.forename: João Pessoa
authors.initials: JP
authors.lastname: Araújo Junior
authors.affiliation: Tropical Diseases Department, Botucatu School of Medicine - UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Erika Alessandra Pellison Nunes
authors.initials: EA
authors.lastname: da Costa
authors.affiliation: Nursing Department, Botucatu School of Medicine - UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Jairo Aparecido
authors.initials: JA
authors.lastname: Ayres
authors.affiliation: Dermatology and Radiotherapy Department, Botucatu School of Medicine - UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Maria Rita Parise
authors.initials: MR
authors.lastname: Fortes
authors.affiliation: Tropical Diseases Department, Botucatu School of Medicine - UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Sueli Aparecida
authors.initials: SA
authors.lastname: Calvi
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D013183:Sputum; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000995:Antitubercular Agents; D016207:Cytokines; C508609:IL10 protein, human; D020381:Interleukin-17; C508960:TGFB1 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II