Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk

dc.creatorBarber, Katrin D. Mayer
dc.creatorAndrade, Bruno de Bezerril
dc.creatorOland, Sandra D
dc.creatorAmaral, Eduardo Pinheiro
dc.creatorBarber, Daniel L
dc.creatorGonzales, Jacqueline
dc.creatorDerrick, Steven C
dc.creatorShi, Ruiru
dc.creatorKumar, Nathella Pavan
dc.creatorWei, Wang
dc.creatorYuan, Xing
dc.creatorZhang, Guolong
dc.creatorCai, Ying
dc.creatorBabu, Subash
dc.creatorCatalfamo, Marta
dc.creatorSalazar, Andres M
dc.creatorVia, Laura E
dc.creatorBarry, Clifton E
dc.creatorSher, Alan
dc.date2018-04-12T18:19:08Z
dc.date2018-04-12T18:19:08Z
dc.date2014
dc.date.accessioned2023-09-26T20:10:56Z
dc.date.available2023-09-26T20:10:56Z
dc.identifierBARBER, K. D. M. et al. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature, 2014
dc.identifier0028-0836
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/25831
dc.identifier10.1038/nature13489
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8850649
dc.descriptionAndrade, Bruno Bezerril. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. 1Immunobiology Section, Laboratory of Parasitic Diseases (LPD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA. 2Department of Immunology, Biomedical Sciences Institutes, University of Sao Paulo, 05508-900 Sao Paulo, Brazil. 3T Lymphocyte Biology Unit, LPD, NIAID, NIH, Bethesda, Maryland 20892, USA. 4Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, NIAID, NIH, Bethesda, Maryland 20892, USA. 5Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. 6Henan Chest Hospital, 450003 Zhengzhou, China. 7NIH, International Center for Excellence in Research, 600 031 Chennai, India. 8National Institute for Research in Tuberculosis (NIRT), 600 031 Chennai, India. 9Sino-US International Research Center for Tuberculosis, and Henan Public Health Center, 450003 Zhengzhou, China. 10Helminth Immunology Section, LPD, NIAID, NIH, Bethesda, Maryland 20892, USA. 11Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland 20892, USA. 12Oncovir Inc., Washington, Washington DC 20008, USA.
dc.descriptionNIAID Intramural Research program and a Concept Acceleration Program-Award
dc.descriptionTuberculosis remains second only to HIV/AIDS as the leading cause of mortality worldwide due to a single infectious agent. Despite chemotherapy, the global tuberculosis epidemic has intensified because of HIV co-infection, the lack of an effective vaccine and the emergence of multi-drug-resistant bacteria. Alternative host-directed strategies could be exploited to improve treatment efficacy and outcome, contain drug-resistant strains and reduce disease severity and mortality. The innate inflammatory response elicited by Mycobacterium tuberculosis (Mtb) represents a logical host target. Here we demonstrate that interleukin-1 (IL-1) confers host resistance through the induction of eicosanoids that limit excessive type I interferon (IFN) production and foster bacterial containment. We further show that, in infected mice and patients, reduced IL-1 responses and/or excessive type I IFN induction are linked to an eicosanoid imbalance associated with disease exacerbation. Host-directed immunotherapy with clinically approved drugs that augment prostaglandin E2 levels in these settings prevented acute mortality of Mtb-infected mice. Thus, IL-1 and type I IFNs represent two major counter-regulatory classes of inflammatory cytokines that control the outcome of Mtb infection and are functionally linked via eicosanoids. Our findings establish proof of concept for host-directed treatment strategies that manipulate the host eicosanoid network and represent feasible alternatives to conventional chemotherapy.
dc.formatapplication/pdf
dc.languageeng
dc.publisherNature Publishing Group
dc.rightsopen access
dc.subjectTuberculose Pulmonar
dc.subjectMycobacterium tuberculosis
dc.subjectInterleucina-1
dc.subjectVacina
dc.subjectInfecção
dc.subjectTuberculosis Pulmonary
dc.subjectMycobacterium tuberculosis
dc.subjectInterleukin-1
dc.subjectVaccine
dc.subjectInfection
dc.titleHost-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk
dc.typeArticle


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