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Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Increased Fas-mediated apoptosis in polymorphonuclear cells from HIV-infected patients
1Institute of Clinical Immunology, University of Los Andes, Mérida, Venezuela.
Abstract:
Neutrophils represent an important line of innate host defence against invading microorganisms and their functional detriment during HIV infection, including accelerated spontaneous cell death, has been shown to contribute to AIDS development. Neutrophils are susceptible to apoptosis via Fas and an interaction between Fas and FasL was suggested originally as a mechanism to explain constitutive neutrophil apoptosis. We have explored some intracellular pathways leading to PMN apoptosis from 28 HIV-infected patients and 24 healthy volunteers. As previously reported, accelerated spontaneous apoptosis was observed in HIV+ patients, but this did not correlate with viral load. Furthermore, an increase in the level of spontaneous apoptosis was detected in neutrophils from HIV-infected patients following inhibition of ERK, suggesting an impairment of this kinase pathway during the early stages of infection which may contribute to PMN dysfunction. An elevated susceptibility to undergo apoptosis was observed following cross-linking of Fas, which correlated both with viral load and co-expression of Fas/FasL surface molecules. Different mechanisms for spontaneous and Fas-induced apoptosis are proposed which together contribute to the neutropenia and secondary infections observed during the progression to AIDS.
Insights
Neutrophils undergo accelerated cell death in HIV infection, impacting innate defense. Impaired ERK signaling and increased Fas-induced apoptosis contribute to this dysfunction and disease progression.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Neutrophils are crucial for innate immunity against pathogens.
- HIV infection is associated with neutrophil dysfunction and accelerated apoptosis, contributing to AIDS.
- Fas and FasL interactions are implicated in neutrophil apoptosis.
Purpose of the Study:
- To investigate intracellular pathways of polymorphonuclear (PMN) apoptosis in HIV-infected patients.
- To explore the role of ERK signaling and Fas-mediated apoptosis in HIV-associated neutropenia.
Main Methods:
- Analysis of PMN apoptosis in 28 HIV-infected patients and 24 healthy volunteers.
- Assessment of spontaneous and Fas-induced apoptosis.
- Inhibition of ERK signaling pathway to evaluate its role in PMN apoptosis.
Main Results:
- Accelerated spontaneous apoptosis was observed in HIV+ patients, independent of viral load.
- Inhibition of ERK signaling increased spontaneous apoptosis in HIV+ neutrophils, suggesting pathway impairment.
- Elevated Fas-induced apoptosis correlated with viral load and Fas/FasL co-expression.
Conclusions:
- Distinct mechanisms underlie spontaneous and Fas-induced apoptosis in HIV-associated PMN dysfunction.
- Impaired ERK signaling may contribute to early-stage PMN dysfunction in HIV infection.
- These apoptotic pathways collectively contribute to neutropenia and secondary infections in AIDS progression.
