TanNatImmunol2008 - A RT I C l e S 2008 Nature Publishing...

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Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling Trupti Kawli & Man-Wah Tan Communication between the immune and nervous systems, each of which is able to react rapidly to environmental stimuli, may confer a survival advantage. However, precisely how the nervous system influences the immune response and whether neural modulation of immune function is biologically important are not well understood. Here we report that neuronal exocytosis of neuropeptides from dense core vesicles suppressed the survival of Caenorhabditis elegans and their clearance of infection with the human bacterial pathogen Pseudomonas aeruginosa . This immunomodulatory function was mediated by INS-7, an insulin-like neuropeptide whose induction was associated with Pseudomonas virulence. INS-7 secreted from the nervous system functioned in a non–cell autonomous way to activate the insulin pathway and alter basal and inducible expression of immunity-related genes in intestinal cells. The cellular and molecular components of the innate immune system pro- vide a critical first line of defense against invading pathogens. The innate immune system consists of two separate but overlapping components: basal immunity and inducible immunity. Basal immunity, which orches- trates the constitutive production of effector molecules such as defensins and other antimicrobial peptides, provides constant and instantaneous protection from pathogens. The inducible component of the innate immune system is activated after detection of a microbe or its product(s). The innate immune system includes factors local to the infected tissue, as well as those produced by neighboring tissues. For study of the latter non–cell autonomous effects, it is especially important to examine host- pathogen interactions in the context of a whole organism. Data indicate that the nervous system, which also is important in the detection of and response to endogenous and exogenous cues, can interact functionally with the innate immune system by hormonal and neuronal routes 1,2 . For example, the sympathetic nervous system regulates systemic immunity through the release of epinephrine, and neurons regulate regional immunity through the release of norepinephrine. Knowledge of how the sympathetic nervous system affects immune function is limited mainly to its effects on adaptive immunity and antibody production 3 . The precise signaling mechanisms and physiological circumstances in which the neuroendocrine system modulates the innate immune system in the context of a whole organism remain poorly defined. Unlike vertebrate and other invertebrate model organisms, most Caenorhabditis elegans mutants with loss of neuronal function are viable and do not have overt defects that severely compromise their survival in laboratory settings 4 . In addition to having a well characterized ner- vous system, C. elegans also has a fairly sophisticated innate immune sys- tem. Genetic and molecular analysis of the innate immune responses
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This note was uploaded on 11/01/2010 for the course A B taught by Professor C during the Spring '10 term at HKU.

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TanNatImmunol2008 - A RT I C l e S 2008 Nature Publishing...

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