TY - JOUR
T1 - Autophagy genes protect against Salmonella typhimurium infection and mediate insulin signaling-regulated pathogen resistance
AU - Jia, Kailiang
AU - Thomas, Collin
AU - Akbar, Muhammad
AU - Sun, Qihua
AU - Adams-Huet, Beverley
AU - Gilpin, Christopher
AU - Levine, Beth
PY - 2009/8/25
Y1 - 2009/8/25
N2 - A conserved insulin-like pathway modulates both aging and pathogen resistance in Caenorhabditis elegans. However, the specific innate effector functions that mediate this pathogen resistance are largely unknown. Autophagy, a lysosomal degradation pathway, plays a role in controlling intracellular bacterial pathogen infections in cultured cells, but less is known about its role at the organismal level. We examined the effects of autophagy gene inactivation on Salmonella enterica Serovar Typhimurium (Salmonella typhimurium) infection in 2 model organisms, Caenorhabditis elegans and Dictyostelium discoideum. In both organisms, genetic inactivation of the autophagy pathway increases bacterial intracellular replication, decreases animal lifespan, and results in apoptotic-independent death. In C. elegans, genetic knockdown of autophagy genes abrogates pathogen resistance conferred by a loss-of-function mutation, daf-2(e1370), in the insulin-like tyrosine kinase receptor or by overexpression of the DAF-16 FOXO transcription factor. Thus, autophagy genes play an essential role in host defense in vivo against an intracellular bacterial pathogen and mediate pathogen resistance in long-lived mutant nematodes.
AB - A conserved insulin-like pathway modulates both aging and pathogen resistance in Caenorhabditis elegans. However, the specific innate effector functions that mediate this pathogen resistance are largely unknown. Autophagy, a lysosomal degradation pathway, plays a role in controlling intracellular bacterial pathogen infections in cultured cells, but less is known about its role at the organismal level. We examined the effects of autophagy gene inactivation on Salmonella enterica Serovar Typhimurium (Salmonella typhimurium) infection in 2 model organisms, Caenorhabditis elegans and Dictyostelium discoideum. In both organisms, genetic inactivation of the autophagy pathway increases bacterial intracellular replication, decreases animal lifespan, and results in apoptotic-independent death. In C. elegans, genetic knockdown of autophagy genes abrogates pathogen resistance conferred by a loss-of-function mutation, daf-2(e1370), in the insulin-like tyrosine kinase receptor or by overexpression of the DAF-16 FOXO transcription factor. Thus, autophagy genes play an essential role in host defense in vivo against an intracellular bacterial pathogen and mediate pathogen resistance in long-lived mutant nematodes.
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U2 - 10.1073/pnas.0813319106
DO - 10.1073/pnas.0813319106
M3 - Article
C2 - 19667176
AN - SCOPUS:70149085849
SN - 0027-8424
VL - 106
SP - 14564
EP - 14569
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 34
ER -