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Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk.
Mayer-Barber, Katrin D; Andrade, Bruno B; Oland, Sandra D; Amaral, Eduardo P; Barber, Daniel L; Gonzales, Jacqueline; Derrick, Steven C; Shi, Ruiru; Kumar, Nathella Pavan; Wei, Wang; Yuan, Xing; Zhang, Guolong; Cai, Ying; Babu, Subash; Catalfamo, Marta; Salazar, Andres M; Via, Laura E; Barry, Clifton E; Sher, Alan.
Afiliação
  • Mayer-Barber KD; Immunobiology Section, Laboratory of Parasitic Diseases (LPD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
  • Andrade BB; Immunobiology Section, Laboratory of Parasitic Diseases (LPD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
  • Oland SD; Immunobiology Section, Laboratory of Parasitic Diseases (LPD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
  • Amaral EP; 1] Immunobiology Section, Laboratory of Parasitic Diseases (LPD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA [2] Department of Immunology, Biomedical Sciences Institutes, University of Sao Paulo, 05508-900 Sao Pau
  • Barber DL; T Lymphocyte Biology Unit, LPD, NIAID, NIH, Bethesda, Maryland 20892, USA.
  • Gonzales J; Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, NIAID, NIH, Bethesda, Maryland 20892, USA.
  • Derrick SC; Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
  • Shi R; Henan Chest Hospital, 450003 Zhengzhou, China.
  • Kumar NP; 1] NIH, International Center for Excellence in Research, 600 031 Chennai, India [2] National Institute for Research in Tuberculosis (NIRT), 600 031 Chennai, India.
  • Wei W; Henan Chest Hospital, 450003 Zhengzhou, China.
  • Yuan X; Henan Chest Hospital, 450003 Zhengzhou, China.
  • Zhang G; Sino-US International Research Center for Tuberculosis, and Henan Public Health Center, 450003 Zhengzhou, China.
  • Cai Y; Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, NIAID, NIH, Bethesda, Maryland 20892, USA.
  • Babu S; 1] NIH, International Center for Excellence in Research, 600 031 Chennai, India [2] Helminth Immunology Section, LPD, NIAID, NIH, Bethesda, Maryland 20892, USA.
  • Catalfamo M; Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland 20892, USA.
  • Salazar AM; Oncovir Inc., Washington, Washington DC 20008, USA.
  • Via LE; Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, NIAID, NIH, Bethesda, Maryland 20892, USA.
  • Barry CE; Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, NIAID, NIH, Bethesda, Maryland 20892, USA.
  • Sher A; Immunobiology Section, Laboratory of Parasitic Diseases (LPD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Nature ; 511(7507): 99-103, 2014 Jul 03.
Article em En | MEDLINE | ID: mdl-24990750
Tuberculosis 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose Pulmonar / Interferon Tipo I / Interleucina-1 / Imunoterapia / Mycobacterium tuberculosis Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Nature Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose Pulmonar / Interferon Tipo I / Interleucina-1 / Imunoterapia / Mycobacterium tuberculosis Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Nature Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos