Posttranslational Regulation of IL-23 Production Distinguishes the Innate Immune Responses to Live Toxigenic versus Heat-Inactivated Vibrio cholerae

Author:

Weil Ana A.12,Ellis Crystal N.1,Debela Meti D.1,Bhuiyan Taufiqur R.3,Rashu Rasheduzzaman3,Bourque Daniel L.1,Khan Ashraful I.3,Chowdhury Fahima3,LaRocque Regina C.12,Charles Richelle C.12,Ryan Edward T.124,Calderwood Stephen B.125,Qadri Firdausi3,Harris Jason B.267

Affiliation:

1. Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachusetts, USA

2. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA

3. Infectious Diseases Division, International Center for Diarrheal Disease and Research, Bangladesh (icddr,b), Dhaka, Bangladesh

4. Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA

5. Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA

6. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA

7. Division of Global Health, Massachusetts General Hospital for Children, Boston, Massachusetts, USA

Abstract

An episode of cholera provides better protection against reinfection than oral cholera vaccines, and the reasons for this are still under study. To better understand this, we compared the immune responses of human cells exposed to live Vibrio cholerae with those of cells exposed to heat-killed V. cholerae (similar to the contents of oral cholera vaccines). We also compared the effects of active cholera toxin and the inactive cholera toxin B subunit (which is included in some cholera vaccines). One key immune signaling molecule, IL-23, was uniquely produced in response to the combination of live bacteria and active cholera holotoxin. Stimulation with V. cholerae that did not produce the active toxin or was killed did not produce an IL-23 response. The stimulation of IL-23 production by cholera toxin-producing V. cholerae may be important in conferring long-term immunity after cholera.

Funder

HHS | National Institutes of Health

HHS | NIH | Fogarty International Center

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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