4.6 Article

Impact of STING Inflammatory Signaling during Intracellular Bacterial Infections

Journal

CELLS
Volume 11, Issue 1, Pages -

Publisher

MDPI
DOI: 10.3390/cells11010074

Keywords

STING; bacteria; type I interferon; infection; inflammation; cyclic dinucleotides

Categories

Funding

  1. Pro-Reitoria de Pesquisa da Universidade Federal de Minas Gerais (PRPQ)
  2. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [303044/2020-9, 406883/2018-1, 465229/2014-0]
  3. Fundaca~o de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) [01945/17]
  4. National Institute of Health (NIH) [R01 AI116453]
  5. [00140-16]

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STING, as an immune sensor, plays a crucial role in the early detection of bacterial pathogens. It activates immune responses by detecting bacterial DNA or cyclic dinucleotides, leading to the production of interferons and proinflammatory cytokines and participating in the metabolic reprogramming of macrophages. However, STING-mediated immune responses during bacterial infections can also be detrimental to the host.
The early detection of bacterial pathogens through immune sensors is an essential step in innate immunity. STING (Stimulator of Interferon Genes) has emerged as a key mediator of inflammation in the setting of infection by connecting pathogen cytosolic recognition with immune responses. STING detects bacteria by directly recognizing cyclic dinucleotides or indirectly by bacterial genomic DNA sensing through the cyclic GMP-AMP synthase (cGAS). Upon activation, STING triggers a plethora of powerful signaling pathways, including the production of type I interferons and proinflammatory cytokines. STING activation has also been associated with the induction of endoplasmic reticulum (ER) stress and the associated inflammatory responses. Recent reports indicate that STING-dependent pathways participate in the metabolic reprogramming of macrophages and contribute to the establishment and maintenance of a robust inflammatory profile. The induction of this inflammatory state is typically antimicrobial and related to pathogen clearance. However, depending on the infection, STING-mediated immune responses can be detrimental to the host, facilitating bacterial survival, indicating an intricate balance between immune signaling and inflammation during bacterial infections. In this paper, we review recent insights regarding the role of STING in inducing an inflammatory profile upon intracellular bacterial entry in host cells and discuss the impact of STING signaling on the outcome of infection. Unraveling the STING-mediated inflammatory responses can enable a better understanding of the pathogenesis of certain bacterial diseases and reveal the potential of new antimicrobial therapy.

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