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Vibrio cholerae O1 Infection Induces Proinflammatory CD4+ T-Cell Responses in Blood and Intestinal Mucosa of Infected Humans▿†

By Alison Kuchta, Taibur Rahman, Erica L. Sennott, Taufiqur R. Bhuyian, Taher Uddin, Rasheduzzaman Rashu, Fahima Chowdhury, Ashraf I. Kahn, Mohammad Arifuzzaman, Ana A. Weil, Michael Podolsky, Regina C. LaRocque, Edward T. Ryan, Stephen B. Calderwood, Firdausi Qadri and Jason B. Harris

Abstract

Vibrio cholerae O1 is a noninvasive enteric pathogen and serves as a model for studies of mucosal immunity. Although symptomatic V. cholerae infection induces durable protection against subsequent disease, vaccination with oral killed whole-cell V. cholerae stimulates less long-lasting protection against cholera. In this study, we demonstrated that cholera induces an early proinflammatory cellular immune response that results in priming of Th1- and Th17-type cytokine responses to ex vivo antigenic stimulation and an increase in the ratio of Th1 to Th2 CD4+ T-cell responses. Comparable priming of Th1 and Th17 responses, with an increased ratio of Th1 to Th2 CD4+ T-cell responses, was not observed in subjects who received two doses of the oral cholera vaccine Dukoral (a whole-cell cholera toxin B subunit containing [WC-CTB] vaccine). These findings suggest that natural V. cholerae infection induces an early, proinflammatory cellular immune response, despite the apparent lack of clinical signs of inflammation. The failure of the WC-CTB vaccine to activate equivalent, CD4+ T-cell responses is a potential explanation for the shorter duration of protection following immunization with this vaccine. Additional studies are needed to determine whether these early T-cell-mediated events predict the subsequent duration of immunologic memory

Topics: Microbial Immunology
Publisher: American Society for Microbiology
OAI identifier: oai:pubmedcentral.nih.gov:3147337
Provided by: PubMed Central
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