Tuberculosis Is Associated with a Down-Modulatory Lung Immune Response That Impairs Th1-Type Immunity
Alexandre S. de Almeida,Patrícia Martins Lago,Neio Boechat,Richard C. Huard,Richard C. Huard,Luiz Claudio Oliveira Lazzarini,Luiz Claudio Oliveira Lazzarini,Adalberto R. Santos,Marcelo Nociari,Hongxia Zhu,Beatriz M. Perez-Sweeney,Heejung Bang,Quanhong Ni,Jie Huang,Andrea L. Gibson,Vera C. Flores,Vera C. Flores,Lorena R. Pecanha,Afrânio Lineu Kritski,José Roberto Lapa e Silva,José Roberto Lapa e Silva,John L. Ho,John L. Ho +22 more
TLDR
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.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.read more
Citations
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The Immune Response in Tuberculosis
Anne O'Garra,Paul S. Redford,Finlay W. McNab,Chloe I Bloom,Robert J. Wilkinson,Matthew Berry +5 more
TL;DR: What the authors know about the immune response in tuberculosis, in human disease, and in a range of experimental models is summarized, all of which are essential to advancing the mechanistic knowledge base of the host-pathogen interactions that influence disease outcome.
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TL;DR: The special physiological relevance of this cytokine lies in the prevention and limitation of over-whelming specific and unspecific immune reactions and, in consequence, of tissue damage.
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The role of IL-10 in immune regulation during M. tuberculosis infection.
TL;DR: It is proposed that IL-10 is linked with the ability of Mtb to evade immune responses and mediate long-term infections in the lung.
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Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes.
TL;DR: Insights into intracellular mechanisms and implications of enhanced pathogenesis after ligation of macrophage Fcγ receptors by infectious immune complexes are reviewed.
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TL;DR: The convergence of intracellular bacterial infections and diabetes poses new challenges for immunologists, providing the impetus for multidisciplinary research.
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