How apoptosis got the immune system in shape

Feig, Christine; Marynen, Peter

doi:10.1002/eji.200737462

Cited by 65 publications

(49 citation statements)

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“…They phagocytose bacteria to eliminate pathogens and may orchestrate the following immune reaction by cytokine release and antigen presentation to the adaptive immune system (6). Under physiological conditions, monocyte activity is terminated by apoptosis (7), mainly induced by phagocytosis and, therefore, called phagocytosis-induced cell death (PICD) (8,9). PICD has been shown to occur after infection with a variety of different pathogens, including Escherichia coli and group-B-Streptococci, two of the main causative agents of neonatal sepsis (9).…”

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Neonatal monocytes express antiapoptotic pattern of Bcl-2 proteins and show diminished apoptosis upon infection with Escherichia coli

et al. 2014

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Background:Neonates show sustained inflammation after a bacterial infection, which is associated with inflammatory diseases like bronchopulmonary dysplasia or periventricular leucomalacia. Physiologically, inflammation is terminated early after the removal of the invading pathogens by phagocytosisinduced cell death (PICD) of immune effector cells. Earlier results showed reduced PICD in neonatal monocytes. The underlying molecular mechanisms are unknown. We hypothesize that the reduced PICD in neonatal monocytes is regulated through the proteins of the B-cell lymphoma 2 (Bcl-2) protein family. Methods: mRNA and protein expression of Bcl-2 family proteins in cord blood and adult peripheral blood monocytes infected with Escherichia coli were analyzed by quantitative real-time PCR and flow cytometry and cytochrome c release by fluorescence microscopy. results: mRNA expression of antiapopototic Bcl-xL was upregulated in cord blood monocytes (CBMO), whereas proapoptotic Bim tended to be higher in peripheral blood monocytes (PBMO). Upon infection, Bax was more strongly expressed in PBMO compared with CBMO. The pro/antiapoptotic balance was skewed toward survival in CBMO and apoptosis in PBMO. Cytochome c release into the cytosol was enhanced in PBMO compared with CBMO. conclusion: Bcl-2 proteins are involved in reduced PICD in neonatal monocytes. These findings are another step toward the understanding of sustained inflammation in neonates.

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Neonatal monocytes express antiapoptotic pattern of Bcl-2 proteins and show diminished apoptosis upon infection with Escherichia coli

et al. 2014

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“…Under physiological conditions, activity of monocytes at sites of infection is terminated by apoptosis (11), mainly induced by a process called phagocytosis-induced cell death (PICD), leading to elimination of activated monocytes (12). PICD seems to be a common event in monocyte-bacteria interaction, given that it has been shown for a huge variety of bacteria, although the signals required to induce apoptosis in this process have not yet been entirely identified (12).…”

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The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates

et al. 2012

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Background:The propensity for sustained inflammation after bacterial infection in neonates, resulting in inflammatory sequelae such as bronchopulmonary dysplasia and periventricular leucomalacia, is well known, but its molecular mechanisms remain elusive. Termination of inflammatory reactions physiologically occurs early after removal of bacteria by phagocytosis-induced cell death (PIcD) of immune effector cells such as monocytes. PIcD from cord blood monocytes (cBMOs) was shown to be reduced as compared with that of peripheral blood monocytes (PBMOs) from adult donors in vitro. Methods: PBMOs, cBMOs, and Fas (cD95)-deficient (lpr) mouse monocytes were analyzed in an in vitro infection model using green fluorescence protein-labeled Escherichia coli (E. coli-GFP). Phagocytosis and apoptosis were quantified by flow cytometry and cD95L secretion was quantified by enzyme-linked immunosorbent assay. results: We demonstrate the involvement of the cD95/ cD95 ligand pathway (cD95/cD95L) in PIcD and provide evidence that diminished cD95L secretion by cBMOs may result in prolonged activation of neonatal immune effector cells. conclusion: These in vitro results offer for the first time a molecular mechanism accounting for sustained inflammation seen in neonates.

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“…Apoptosis can be either Ag-dependent, initiated by death receptor signaling and/or activating intracellular pathways, or it may occur by negligence when Ag-specific receptors are not stimulated. When the cellular microenvironment is depleted of survival factors, another type of programmed cell death occurs, a phenomenon known as authophagy (Lemasters 2005, Feig & Peter 2007. Moreover, modulation of programmed cell death plays an important role in several pathologies related to viral infections such as AIDS and measles (Oyaizu & Pahwa 1995, Servet-Delprat et al 2000.…”

Section: Discussionmentioning

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“…After signaling, an enzymatic cascade leads to the activation of a series of cysteinyl aspartate proteases known as caspases (Feig & Peter 2007) and then to cell degredation. However, the apoptotic process can be triggered by endogenous events as well.…”

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Dengue-2 infection and the induction of apoptosis in human primary monocytes

Torrentes-Carvalho

Azeredo

Reis

et al. 2009

Mem. Inst. Oswaldo Cruz

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Monocytes/macrophages are important targets for dengue virus (DENV) replication; they induce inflammatory mediators and are sources of viral dissemination in the initial phase of the disease. Apoptosis is an active process of cellular destruction genetically regulated, in which a complex enzymatic pathway is activated and may be trigged by many viral infections. Since the mechanisms of apoptotic induction in DENV-infected target cells are not yet defined, we investigated the virus-cell interaction using a model of primary human monocyte infection with DENV-2 with the aim of identifying apoptotic markers. Cultures analyzed by flow cytometry and confocal microscopy yielded DENV antigen positive cells with rates that peaked at the second day post infection (p.i.), decayed afterwards and produced the apoptosis-related cytokines TNF-α and IL-10. Phosphatidylserine, an early marker for apoptosis, was increased at the cell surface and the Fas death receptor was upregulated at the second day p.i. at significantly higher rates in DENV infected cell cultures than controls. However, no detectable changes were observed in the expression of the anti-apoptotic protein Bcl-2 in infected cultures. Our data support virus modulation of extrinsic apoptotic factors in the in vitro model of human monocyte DENV-2 infection. DENV may be interfering in activation and death mechanisms by inducing apoptosis in target cells.Key words: dengue -apoptosis -monocytes -human The dengue fever emergency has become one of the most dramatic public health issues in Latin America. Epidemics are presenting increased severity and frequency and are continuously expanding geographically (Gubler 2002). In Brazil, the disease is endemic and during the last five years the region has accounted for 70% reported cases in the Americas (Nogueira et al. 2007). Infection with the Dengue virus (DENV) causes a disease spectrum ranging from asymptomatic to shock and hemorrhages, with a risk of lethality. Acute vascular permeability may be followed by abnormal vascular homeostasis. Clinical manifestations include plasmatic leakage, bleeding tendency and liver commitment followed by mild seric transaminase elevation. The physiopathology of the disease may be explained as result of infected monocyte activation by the production of factors that act to increase the vascular permeability and disturb the coagulation system. Pleural effusion, ascites and hemoconcentration are signs of intravascular volume loss. Such factors promote rapid progression to shock (Gibbons & Vaughn 2002).Mononuclear phagocytes are considered the main targets for viral replication (Jessie et al. 2004, NevesSouza et al. 2005). Cells such as B lymphocytes, monocytes, hepatocytes and dendritic cells are described as potential virus targets and may undergo programmed cell death when infected in culture. Reports show apoptotic induction in DENV infected endothelial cells elevates IL-8 and RANTES production, which are chemokines related to inflammatory processes during cell migration (Avirutnan et al. 1...

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How apoptosis got the immune system in shape

Cited by 65 publications

References 93 publications

Neonatal monocytes express antiapoptotic pattern of Bcl-2 proteins and show diminished apoptosis upon infection with Escherichia coli

Neonatal monocytes express antiapoptotic pattern of Bcl-2 proteins and show diminished apoptosis upon infection with Escherichia coli

The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates

Dengue-2 infection and the induction of apoptosis in human primary monocytes

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