Nod proteins link bacterial sensing and autophagy.
Autophagy is one of the main cellular degradation systems in eukaryotes, responsible for the elimination of long-lived proteins and damaged organelles. Besides its well-documented role as a housekeeping mechanism, autophagy has recently caught the attention of groups working in the fields of microbiology and immunology, especially those working in innate immunity. In particular, the highly specific segregation and degradation of intracellular bacteria by the autophagic machinery was a matter of great interest. However, it was still unclear how the autophagy machinery could target intracellular bacteria with such specificity. We have recently analyzed the role of the intracellular peptidoglycan (PG) receptors Nod1 and Nod2 as a link between intracellular bacterial sensing and the induction of autophagy. Our results demonstrated that Nod2 recruits the critical autophagy protein ATG16L1 to the plasma membrane during bacterial invasion and that cells expressing mutations in these proteins--two of the most important associated with Crohn disease--autophagy is defective upon infection or stimulation with the bacterial peptidoglycan fragment MDP. Thus, our findings put together two genes previously reported as independent risk factors for the development of Crohn disease and open a venue in the study of new therapies to cure the disease.
Travassos
Leonardo H
LH
Department of Immunology, University of Toronto, Toronto, ON, Canada.
Carneiro
Leticia A M
LA
Girardin
Stephen
S
Philpott
Dana J
DJ
D000818:Animals; D001343:Autophagy / Q000276:immunology*; D000071183:Autophagy-Related Proteins; D001419:Bacteria / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D006801:Humans; D051379:Mice; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology*
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein