Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis

Lu, Qun; Yokoyama, Christine C.; Williams, Jesse W.; Baldridge, Megan T.; Jin, Xiaohua; DesRochers, Brittany L.; Bricker, Traci L.; Wilen, Craig B.; Bagaitkar, Juhi; Loginicheva, Ekaterina; Sergushichev, Alexey; Kreamalmeyer, Darren; Keller, Brian C.; Zhao, Yan; Kambal, Amal; Green, Douglas R.; Martinez, Jennifer; Dinauer, Mary C.; Holtzman, Michael J.; Crouch, Erika C.; Beatty, Wandy L.; Boon, Adrianus C. M.; Zhang, Hong; Randolph, Gwendalyn J.; Artyomov, Maxim N.; Virgin, Herbert W.

doi:10.1016/j.chom.2015.12.011

Cited by 88 publications

(95 citation statements)

References 79 publications

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“…We believe that this seemingly contradictory finding may reflect the function of certain autophagy genes to inhibit inflammation, as seen in tissue-specific knock-out animal models of autophagy genes resulting in wide spread tissue over-inflammation [27,28]. In fact, in in vivo cancer models, autophagy inhibition has been demonstrated to favor immunosuppression, leading to increased tumor aggressiveness [29].…”

Section: Discussionmentioning

confidence: 99%

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

Chu¹,

Thamotharan²,

Ganguly³

et al. 2016

Nutrition Research

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Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often results in short- and long- term sequelae for offspring. The mechanisms underlying IUGR are poorly understood, but it is known that healthy placentation is essential for nutrient provision to fuel fetal growth, and is regulated by immunologic inputs. We hypothesized that in pregnancy, maternal food restriction (FR) resulting in IUGR would decrease the overall immunotolerant milieu in the placenta, leading to increased cellular stress and death. Our specific objectives were to evaluate: (1) key cytokines (e.g. IL10) that regulate maternal-fetal tolerance, (2) cellular processes (autophagy and ER stress) that are immunologically-mediated and important for cellular survival and functioning, and (3) evaluate the resulting IUGR phenotype and placental histopathology. After subjecting pregnant mice to mild and moderate FR from gestational day (GD) 10 to 19, we collected placentas and embryos at GD19. We examined RNA sequencing data to identify immunologic pathways affected in IUGR-associated placentas and validated mRNA expression changes of genes important in cellular integrity. We also evaluated histopathologic changes in vascular and trophoblastic structures as well as protein expression changes in autophagy, ER stress, and apoptosis in the mouse placentas. Several differentially expressed genes were identified in FR compared to control mice, including a considerable subset that regulates immune tolerance, inflammation and cellular integrity. In summary, maternal food restriction decreases anti-inflammatory effect of IL10 and suppresses placental autophagic and ER stress responses, despite evidence of dysregulated vascular and trophoblast structures leading to IUGR.

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Section: Discussionmentioning

confidence: 99%

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

Chu¹,

Thamotharan²,

Ganguly³

et al. 2016

Nutrition Research

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show abstract

“…of latent murine herpesvirus 68 (MHV68) [24][25][26] . The enhanced host defence in these models is associated with large scale increases in cytokine levels and/or inflammatory gene expression.…”

Section: Pyroptosismentioning

confidence: 99%

Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis

2016

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Autophagy has broad functions in immunity ranging from cell autonomous defense to coordination of complex multicellular responses. The successful resolution of infection and avoidance of autoimmunity necessitates efficient and timely communication between autophagy and pathways that sense the immune environment. In this article, progress in elucidating mechanisms of crosstalk between autophagy and inflammatory signaling cascades will be reviewed. The recent literature indicates that a variety of immune mediators induce or repress autophagy. It is also becoming increasing clear that immune signaling cascades are subject to regulation by autophagy, and that a return to homeostasis following a robust immune response is critically dependent on this pathway. Importantly, examples of non-canonical forms of autophagy in mediating immunity are pervasive. Improved mechanistic understanding of the autophagy machinery offers hope for treating infectious and inflammatory diseases.

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“…8-12 week old mice were anesthetized and inoculated with 50 TCID 50 H1N1 influenza virus strain PR8 IN, as described (76). Mice losing more than 30% of their initial body weight were sacrificed.…”

Section: Lps Treatmentsmentioning

confidence: 99%

LysMD3 is a type II membrane protein without an role in the response to a range of pathogens

Yokoyama

Baldridge

Leung

et al. 2018

Journal of Biological Chemistry

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Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis

Cited by 88 publications

References 79 publications

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis

LysMD3 is a type II membrane protein without an role in the response to a range of pathogens

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