Baxt, Leigh A.Goldberg, Marcia2014-05-062014Baxt, Leigh A., and Marcia B. Goldberg. 2014. “Host and Bacterial Proteins That Repress Recruitment of LC3 to Shigella Early during Infection.” PLoS ONE 9 (4): e94653. doi:10.1371/journal.pone.0094653. http://dx.doi.org/10.1371/journal.pone.0094653.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:12152839Shigella spp. are intracytosolic gram-negative pathogens that cause disease by invasion and spread through the colonic mucosa, utilizing host cytoskeletal components to form propulsive actin tails. We have previously identified the host factor Toca-1 as being recruited to intracellular S. flexneri and being required for efficient bacterial actin tail formation. We show that at early times during infection (40 min.), the type three-secreted effector protein IcsB recruits Toca-1 to intracellular bacteria and that recruitment of Toca-1 is associated with repression of recruitment of LC3, as well as with repression of recruitment of the autophagy marker NDP52, around these intracellular bacteria. LC3 is best characterized as a marker of autophagosomes, but also marks phagosomal membranes in the process LC3-associated phagocytosis. IcsB has previously been demonstrated to be required for S. flexneri evasion of autophagy at late times during infection (4–6 hr) by inhibiting binding of the autophagy protein Atg5 to the Shigella surface protein IcsA (VirG). Our results suggest that IcsB and Toca-1 modulation of LC3 recruitment restricts LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants. Together with published results, our findings suggest that IcsB inhibits innate immune responses in two distinct ways, first, by inhibiting LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants early during infection, and second, by inhibiting autophagy late during infection.en-USBiology and Life SciencesImmunologyImmune SystemInnate Immune SystemImmunityMicrobiologyBacteriologyGram NegativeMedical MicrobiologyMicrobial PathogensBacterial PathogensMedicine and Health SciencesInfectious DiseasesPathology and Laboratory MedicinePathogenesisHost-Pathogen InteractionsJournal Article2014-05-0610.1371/journal.pone.0094653