p53 integrates host defense and cell fate during bacterial pneumonia

Madenspacher, Jennifer H.; Azzam, Kathleen M.; Gowdy, Kymberly M.; Malcolm, Kenneth C.; Nick, Jerry A.; Dixon, Darlene; Aloor, Jim J.; Draper, David E.; Guardiola, John; Shatz, Maria; Menéndez, Daniel; Lowe, Julie M.; Lü, Jun; Bushel, Pierre R.; Li, Leping; Merrick, B. Alex; Resnick, Michael A.; Fessler, Michael B.

doi:10.1084/jem.20121674

Cited by 53 publications

(42 citation statements)

References 57 publications

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“…For example, miR-33 was recently reported to repress the tumor suppressor p53 (50); we and others have reported that p53-deficient mice display enhanced proinflammatory gene expression in response to LPS due to derepression of NF-B (51,52). Alternatively, the potential for miR-33 to suppress inflammation in some contexts is also suggested by a recent report that miR-33 represses the NF-B co-activator receptor-interacting protein-140 (53).…”

Section: Mir-33 Regulates the Innate Immune Responsementioning

confidence: 84%

MicroRNA-33 Regulates the Innate Immune Response via ATP Binding Cassette Transporter-mediated Remodeling of Membrane Microdomains

Lai

Azzam

Lin

et al. 2016

Journal of Biological Chemistry

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MicroRNAs (miRNAs) 3 are small (ϳ22-nucleotide) noncoding RNAs that regulate gene expression by binding to partially complementary sites in the 3Ј-untranslated regions (UTRs) of specific mRNAs, thereby promoting degradation and/or repressing translation of target mRNAs. The human genome contains Ͼ2500 unique mature miRNAs (1). Because individual miRNAs typically have multiple targets, it is thought that Ͼ60% of all human genes may be subject to regulation by miRNAs (2). The promiscuity of miRNAs for target RNAs is expected to represent a fundamental mechanism of cross-talk and coordination among signaling networks in development, health, and disease.Among the signaling networks that have been shown in recent years to be regulated by miRNAs are the Toll-like receptors (TLRs) of the innate immune system. Multiple TLRs up-regulate miRNAs, including miR-155, miR-146, miR-21, miR-147, and miR-9, whereas activation of TLR4 by lipopolysaccharide (LPS) down-regulates a distinct set of miRNAs (3, 4). In turn, miRNAs "fine tune" the proinflammatory signaling output of TLR cascades by controlling the expression of TLR pathway members (3, 4). Thus, miR-146 suppresses signaling by multiple TLRs via targeting the common signaling hubs IL-1 receptor-associated kinase 1 and TNF receptor-associated factor 6 (5), whereas miR-155 has complex effects, repressing the TLR adaptor myeloid differentiation primary response 88 (MyD88) (6, 7) and TAK1-binding protein 2 (8), an upstream activator of the mitogen-activated protein kinases, but also promoting cytokine expression through actions on other targets (3). Although virtually all known examples of TLR regulation by miRNAs operate through direct targeting of TLR pathway components, it is expected that miRNAs may also indirectly impact the innate immune response by regulating other networks that cross-talk with TLRs.miR-33a and miR-33b (present in primates but absent in rodents and lower species in which miR-33a is simply referred to as "miR-33") are now known to be master regulators of cho-

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Section: Mir-33 Regulates the Innate Immune Responsementioning

confidence: 84%

MicroRNA-33 Regulates the Innate Immune Response via ATP Binding Cassette Transporter-mediated Remodeling of Membrane Microdomains

Lai

Azzam

Lin

et al. 2016

Journal of Biological Chemistry

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“…The DNA damage responses orchestrated by ATM 17 and by p53 165 confer tissue damage control and disease tolerance to pulmonary bacterial infections in mice. Damage to cellular organelles in countered by the autophagy response.…”

Section: Box 3 Microbiota and Disease Tolerancementioning

confidence: 99%

Disease tolerance and immunity in host protection against infection

2017

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The immune system has most likely evolved to limit the negative impact exerted by pathogens on host homeostasis. This defense strategy relies on the concerted action of innate and adaptive components of the immune system, which sense and target pathogens for containment, destruction or expulsion. Resistance to infection refers to these immune functions, which reduce the pathogen load of an infected host as the means to preserve homeostasis. Immune-driven resistance to infection is coupled to an additional, and arguably as important, defense strategy that limits the extent of dysfunction imposed to host parenchyma tissues during infection, without exerting a direct negative impact on pathogens.This defense strategy, called disease tolerance, relies on tissue damage control mechanisms that prevent the deleterious effects of pathogens, while uncoupling immunedriven resistance mechanisms from immunopathology and disease. Here we provide a unifying view of resistance and disease tolerance within the framework of immunity to infection.

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“…Temperature and humidity of chamber air were monitored continuously, as was the O 3 concentration with a Teledyne T400 ultraviolet light photometer. BALF was collected immediately following sacrifice, and cell counts were performed as described previously (74). Protein analysis was performed using BCA protein assay (Pierce).…”

Section: Sterol Profiling Using Ptad Derivatization and Lc-selectedmentioning

confidence: 99%

Ozone-derived Oxysterols Affect Liver X Receptor (LXR) Signaling

Speen

Kim

Bauer

et al. 2016

Journal of Biological Chemistry

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p53 integrates host defense and cell fate during bacterial pneumonia

Abstract: p53 deletion augments neutrophil-mediated bacterial clearance in the lung at the expense of tissue homeostasis, leading to increased mortality.

Cited by 53 publications

References 57 publications

MicroRNA-33 Regulates the Innate Immune Response via ATP Binding Cassette Transporter-mediated Remodeling of Membrane Microdomains

MicroRNA-33 Regulates the Innate Immune Response via ATP Binding Cassette Transporter-mediated Remodeling of Membrane Microdomains

Disease tolerance and immunity in host protection against infection

Ozone-derived Oxysterols Affect Liver X Receptor (LXR) Signaling

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