Consequence of Enhanced LC3-trafficking for a Live, Attenuated M. Tuberculosis Vaccine

Overview

Journal Vaccine

Specialty Allergy & Immunology

Date 2018 Jan 19

PMID 29343411

Citations 8

Authors

Stefan Koster

Thais Klevorn

Kadamba Papavinasasundaram

Christopher M Sassetti

Cynthia Portal-Celhay

Jennifer A Philips

Affiliations

Soon will be listed here.

Abstract

Development of a new vaccine against tuberculosis is urgently needed. Recent work has demonstrated that two related LC3-associated trafficking pathways, autophagy and LC3-associated phagocytosis (LAP), enhance antigen presentation and might play a role in vaccine efficacy. Mycobacterium tuberculosis inhibits both LC3-trafficking pathways. Moreover, the vaccine strain, BCG, induces even less LC3-trafficking than M. tuberculosis, which may help explain its limited efficacy. To determine whether enhanced LC3-trafficking can improve efficacy of a live, attenuated M. tuberculosis vaccine, we took advantage of our recent finding that the bacterial virulence factor CpsA inhibits LAP. When we deleted cpsA in the mc6206 vaccine strain, it dramatically increased LC3-trafficking. We compared the protective efficacy of the strain lacking cpsA to the parent strain and to BCG in mice challenged with M. tuberculosis. We found that the strain lacking cpsA generated modestly enhanced protection in the spleen, but overall did not outperform BCG.

Citing Articles

Live Attenuated Vaccines against Tuberculosis: Targeting the Disruption of Genes Encoding the Secretory Proteins of Mycobacteria.

Veerapandian R, Gadad S, Jagannath C, Dhandayuthapani S Vaccines (Basel). 2024; 12(5).

PMID: 38793781 PMC: 11126151. DOI: 10.3390/vaccines12050530.

CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis.

Grigsby S, Prasad G, Wallach J, Mittal E, Hsu F, Schnappinger D Cell Rep. 2023; 43(1):113607.

PMID: 38127624 PMC: 10900767. DOI: 10.1016/j.celrep.2023.113607.

Advance in strategies to build efficient vaccines against tuberculosis.

Qu W, Guo Y, Xu Y, Zhang J, Wang Z, Ding C Front Vet Sci. 2022; 9:955204.

PMID: 36504851 PMC: 9731747. DOI: 10.3389/fvets.2022.955204.

LC3-Associated Phagocytosis in Bacterial Infection.

Yuan J, Zhang Q, Chen S, Yan M, Yue L Pathogens. 2022; 11(8).

PMID: 36014984 PMC: 9415076. DOI: 10.3390/pathogens11080863.

LC3-Associated Phagocytosis and the Arms Race Against Bacterial Pathogens.

Grijmans B, van der Kooij S, Varela M, Meijer A Front Cell Infect Microbiol. 2022; 11:809121.

PMID: 35047422 PMC: 8762105. DOI: 10.3389/fcimb.2021.809121.

References

Grode L, Seiler P, Baumann S, Hess J, Brinkmann V, Eddine A . Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. J Clin Invest. 2005; 115(9):2472-9. PMC: 1187936. DOI: 10.1172/JCI24617. View

Romao S, Gasser N, Becker A, Guhl B, Bajagic M, Vanoaica D . Autophagy proteins stabilize pathogen-containing phagosomes for prolonged MHC II antigen processing. J Cell Biol. 2013; 203(5):757-66. PMC: 3857489. DOI: 10.1083/jcb.201308173. View

Martinez J, Malireddi R, Lu Q, Cunha L, Pelletier S, Gingras S . Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat Cell Biol. 2015; 17(7):893-906. PMC: 4612372. DOI: 10.1038/ncb3192. View

Koster S, Upadhyay S, Chandra P, Papavinasasundaram K, Yang G, Hassan A . is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA. Proc Natl Acad Sci U S A. 2017; 114(41):E8711-E8720. PMC: 5642705. DOI: 10.1073/pnas.1707792114. View

Sambandamurthy V, Derrick S, Hsu T, Chen B, Larsen M, Jalapathy K . Mycobacterium tuberculosis DeltaRD1 DeltapanCD: a safe and limited replicating mutant strain that protects immunocompetent and immunocompromised mice against experimental tuberculosis. Vaccine. 2006; 24(37-39):6309-20. DOI: 10.1016/j.vaccine.2006.05.097. View

Watson R, Manzanillo P, Cox J . Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell. 2012; 150(4):803-15. PMC: 3708656. DOI: 10.1016/j.cell.2012.06.040. View

Ng T, Saavedra-Avila N, Kennedy S, Carreno L, Porcelli S . Current efforts and future prospects in the development of live mycobacteria as vaccines. Expert Rev Vaccines. 2015; 14(11):1493-507. PMC: 4888961. DOI: 10.1586/14760584.2015.1089175. View

Gengenbacher M, Nieuwenhuizen N, Kaufmann S . BCG - old workhorse, new skills. Curr Opin Immunol. 2017; 47:8-16. DOI: 10.1016/j.coi.2017.06.007. View

Huang J, Brumell J . Bacteria-autophagy interplay: a battle for survival. Nat Rev Microbiol. 2014; 12(2):101-14. PMC: 7097477. DOI: 10.1038/nrmicro3160. View

10.

Portal-Celhay C, Tufariello J, Srivastava S, Zahra A, Klevorn T, Grace P . Mycobacterium tuberculosis EsxH inhibits ESCRT-dependent CD4 T-cell activation. Nat Microbiol. 2016; 2:16232. PMC: 5453184. DOI: 10.1038/nmicrobiol.2016.232. View

11.

Gengenbacher M, Nieuwenhuizen N, Vogelzang A, Liu H, Kaiser P, Schuerer S . Deletion of nuoG from the Vaccine Candidate Mycobacterium bovis BCG ΔureC::hly Improves Protection against Tuberculosis. mBio. 2016; 7(3). PMC: 4895111. DOI: 10.1128/mBio.00679-16. View

12.

Stanley S, Cox J . Host-pathogen interactions during Mycobacterium tuberculosis infections. Curr Top Microbiol Immunol. 2013; 374:211-41. DOI: 10.1007/82_2013_332. View

13.

Mehra A, Zahra A, Thompson V, Sirisaengtaksin N, Wells A, Porto M . Mycobacterium tuberculosis type VII secreted effector EsxH targets host ESCRT to impair trafficking. PLoS Pathog. 2013; 9(10):e1003734. PMC: 3814348. DOI: 10.1371/journal.ppat.1003734. View

14.

Sambandamurthy V, Derrick S, Jalapathy K, Chen B, Russell R, Morris S . Long-term protection against tuberculosis following vaccination with a severely attenuated double lysine and pantothenate auxotroph of Mycobacterium tuberculosis. Infect Immun. 2005; 73(2):1196-203. PMC: 547051. DOI: 10.1128/IAI.73.2.1196-1203.2005. View

15.

Ravindran R, Khan N, Nakaya H, Li S, Loebbermann J, Maddur M . Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation. Science. 2013; 343(6168):313-317. PMC: 4048998. DOI: 10.1126/science.1246829. View

16.

Gutierrez M, Master S, Singh S, Taylor G, Colombo M, Deretic V . Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell. 2004; 119(6):753-66. DOI: 10.1016/j.cell.2004.11.038. View

17.

Miller J, Velmurugan K, Cowan M, Briken V . The type I NADH dehydrogenase of Mycobacterium tuberculosis counters phagosomal NOX2 activity to inhibit TNF-alpha-mediated host cell apoptosis. PLoS Pathog. 2010; 6(4):e1000864. PMC: 2858756. DOI: 10.1371/journal.ppat.1000864. View

18.

Jagannath C, Lindsey D, Dhandayuthapani S, Xu Y, Hunter Jr R, Eissa N . Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nat Med. 2009; 15(3):267-76. DOI: 10.1038/nm.1928. View

19.

Munz C . Autophagy Beyond Intracellular MHC Class II Antigen Presentation. Trends Immunol. 2016; 37(11):755-763. DOI: 10.1016/j.it.2016.08.017. View