Open AccessTrade‐offs between longevity and pathogen resistance in Drosophila melanogaster are mediated by NFκB signaling
Author(s) -
Libert Sergiy,
Chao Yufang,
Chu Xiaowen,
Pletcher Scott D.
Publication year - 2006
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2006.00251.x
Subject(s) - biology , longevity , innate immune system , drosophila melanogaster , immune system , immunity , effector , inflammation , phenotype , melanogaster , pathogen , acquired immune system , immunology , microbiology and biotechnology , signal transduction , genetics , gene
Summary The innate immune response protects numerous organisms, including humans, from the universe of pathogenic molecules, viruses and micro‐organisms. Despite its role in promoting pathogen resistance, inappropriate activation and expression of NFκB and other immunity‐related effector molecules can lead to cancer, inflammation, and other diseases of aging. Understanding the mechanisms leading to immune system activation as well as the short‐ and long‐term consequences of such activation on health and lifespan is therefore critical for the development of beneficial immuno‐modulating and longevity‐promoting interventions. Mechanisms of innate immunity are highly conserved across species, and we take advantage of genetic tools in the model organism, Drosophila melanogaster , to study the effects of acute and chronic activation of immunity pathways on pathogen resistance and general fitness of adult flies. Our findings indicate that fat body specific overexpression of a putative pathogen recognition molecule, peptidoglycan recognition protein (PGRP‐LE), is sufficient for constitutive up‐regulation of the immune response and for enhanced pathogen resistance. Primary components of fitness are unaffected by acute activation, but chronic activation leads to an inflammatory state and reduced lifespan. These phenotypes are dependent on the NFκB‐related transcriptional factor, Relish, and they establish a mechanistic basis for a link between immunity, inflammation, and longevity.