scholarly journals Dissection of the Interplay between Class I PI3Ks and Rac Signaling in Phagocytic Functions

2010 ◽  
Vol 10 ◽  
pp. 1826-1839 ◽  
Author(s):  
Carlotta Costa ◽  
Giulia Germena ◽  
Emilio Hirsch
Keyword(s):  
Reactive Oxygen Species ◽  
Immune Response ◽  
Innate Immunity ◽  
Reactive Oxygen Species Production ◽  
Molecular Mechanisms ◽  
Oxygen Species ◽  
The Core ◽  
Rac Gtpases ◽  
Lipid Kinases ◽  
Species Production

Phagocytes, like neutrophils and macrophages, are specialized cells evolved to clear infectious pathogens. This function resides at the core of innate immunity and requires a series of concerted events that lead first to migration to the infected tissue and then to the killing of the invading pathogens. Molecular mechanisms underlying these processes are starting to emerge and point to the interplay between two families of crucial proteins: the PI3K lipid kinases and the Rac GTPases. This review focuses on how these two protein families contribute to migration, phagocytosis, and reactive oxygen species production, as well as their epistatic and feedback relations that finely tune these crucial aspects of the immune response.

scholarly journals Ubiquitination of Listeria Virulence Factor InlC Contributes to the Host Response to Infection

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Edith Gouin ◽  
Damien Balestrino ◽  
Orhan Rasid ◽  
Marie-Anne Nahori ◽  
Véronique Villiers ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Immune Response ◽  
Listeria Monocytogenes ◽  
Host Response ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Pathogenic Potential ◽  
Content Type ◽  
Species Production

ABSTRACT Listeria monocytogenes is a pathogenic bacterium causing potentially fatal foodborne infections in humans and animals. While the mechanisms used by Listeria to manipulate its host have been thoroughly characterized, how the host controls bacterial virulence factors remains to be extensively deciphered. Here, we found that the secreted Listeria virulence protein InlC is monoubiquitinated by the host cell machinery on K224, restricting infection. We show that the ubiquitinated form of InlC interacts with the intracellular alarmin S100A9, resulting in its stabilization and in increased reactive oxygen species production by neutrophils in infected mice. Collectively, our results suggest that posttranslational modification of InlC exacerbates the host response upon Listeria infection. IMPORTANCE The pathogenic potential of Listeria monocytogenes relies on the production of an arsenal of virulence determinants that have been extensively characterized, including surface and secreted proteins of the internalin family. We have previously shown that the Listeria secreted internalin InlC interacts with IκB kinase α to interfere with the host immune response (E. Gouin, M. Adib-Conquy, D. Balestrino, M.-A. Nahori, et al., Proc Natl Acad Sci USA, 107:17333–17338, 2010, https://doi.org/10.1073/pnas.1007765107). In the present work, we report that InlC is monoubiquitinated on K224 upon infection of cells and provide evidence that ubiquitinated InlC interacts with and stabilizes the alarmin S100A9, which is a critical regulator of the immune response and inflammatory processes. Additionally, we show that ubiquitination of InlC causes an increase in reactive oxygen species production by neutrophils in mice and restricts Listeria infection. These findings are the first to identify a posttranscriptional modification of an internalin contributing to host defense.

Effect of denervation on mitochondrially mediated apoptosis in skeletal muscle

2007 ◽  
Vol 102 (3) ◽  
pp. 1143-1151 ◽  
Author(s):  
Peter J. Adhihetty ◽  
Michael F. N. O'Leary ◽  
Beatrice Chabi ◽  
Karen L. Wicks ◽  
David A. Hood
Keyword(s):  
Reactive Oxygen Species ◽  
Muscle Atrophy ◽  
Reactive Oxygen Species Production ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Mitochondrial Content ◽  
Peroxisome Proliferator Activated Receptor ◽  
Species Production

Chronic muscle disuse induced by denervation reduces mitochondrial content and produces muscle atrophy. To investigate the molecular mechanisms responsible for these adaptations, we assessed 1) mitochondrial biogenesis- and apoptosis-related proteins and 2) apoptotic susceptibility and cell death following denervation. Rats were subjected to 5, 7, 14, 21, or 42 days of unilateral denervation of the sciatic or peroneal nerve. Muscle mass and mitochondrial content were reduced by 40–65% after 21 and 42 days of denervation. Denervation-induced decrements in mitochondrial content occurred along with 60% and 70% reductions in transcription factor A (Tfam) and peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, respectively. After 42 days of denervation, Bax was elevated by 115% and Bcl-2 was decreased by 89%, producing a 16-fold increase in the Bax-to-Bcl-2 ratio. Mitochondrial reactive oxygen species production was markedly elevated by 5- to 7.5-fold in subsarcolemmal mitochondria after 7, 14, and 21 days of denervation, whereas reactive oxygen species production in intermyofibrillar (IMF) mitochondria was reduced by 40–50%. Subsarcolemmal and IMF mitochondrial levels of MnSOD were also reduced by 40–50% after 14–21 days of denervation. The maximal rate of IMF mitochondrial pore opening ( Vmax) was elevated by 25–35%, and time to Vmax was reduced by 20–25% after 14 and 21 days, indicating increased apoptotic susceptibility. Myonuclear decay, assessed by DNA fragmentation, was elevated at 7–21 days of denervation. Our data indicate that PGC-1α and Tfam are important factors that likely contribute to the reduced mitochondrial content after chronic disuse. In addition, our results illustrate that, despite the reduced mitochondrial content, denervated muscle has greater mitochondrial apoptotic susceptibility, which coincided with elevated apoptosis, and these processes may contribute to denervation-induced muscle atrophy.

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