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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Host-directed therapy of tuberculosis based on interleukin-1 and type i interferon crosstalk
Nature, Volume 511, No. 7507, Year 2014
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Description
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. © 2014 Macmillan Publishers Limited.
Authors & Co-Authors
Mayer-Barber, Katrin D.
United States, Bethesda
National Institutes of Health Nih
Andrade, Bruno B.
United States, Bethesda
National Institutes of Health Nih
Amaral, Eduardo Pinheiro
United States, Bethesda
National Institutes of Health Nih
Brazil, Sao Paulo
Universidade de São Paulo
Barber, Daniel L.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Gonzales, Jacqueline
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Shi, Ruiru
China, Zhengzhou
Henan Chest Hospital
Kumar, Nathella Pavan
India, Chennai
Tuberculosis Research Centre India
Wei, Wang
China, Zhengzhou
Henan Chest Hospital
Yuan, Xing
China, Zhengzhou
Henan Chest Hospital
Zhang, Guolong
China, Zhengzhou
Sino-us International Research Center of Tuberculosis
Cai, Ying
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Babu, Subash S.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Salazar, Andrés Mario
Unknown Affiliation
Via, L. E.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Barry, Clifton Earl
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Sher, Alan F.
United States, Bethesda
National Institutes of Health Nih
Statistics
Citations: 551
Authors: 16
Affiliations: 7
Identifiers
Doi:
10.1038/nature13489
ISSN:
00280836
Research Areas
Cancer
Infectious Diseases