Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response

David W. Pascual, David M. Hone, Stacy Hall, Frederik W. Van Ginkel, Masafumi Yamamoto, Nancy Walters, Kohataro Fujihashi, Robert J. Powell, Shaoguang Wu, John L. Vancott, Hiroshi Kiyono, Jerry R. Mcghee

Research output: Contribution to journalArticle

Abstract

Protective immunity to enterotoxigenic Escherichia coli (ETEC) is antibody (Ab) dependent; however, oral immunization with purified ETEC fimbriae fails to elicit protective immunity as a consequence of antigenic alteration by the gastrointestinal (GI) tract. Unless unaltered ETEC fimbriae can reach the inductive lymphoid tissues of the GI tract, immunity to ETEC cannot be induced. To produce immunity, live vectors, such as Salmonella typhimurium, can effectively target passenger antigens to the inductive lymphoid tissues of the GI tract. By convention, oral immunizations with Salmonella vectors induce CD4+ T helper (Th) cell responses by gamma interferon (IFN-γ)-dominated pathways both to the vector and passenger antigen, resulting in serum immunoglobulin G2a (IgG2a) and modest mucosal IgA Ab responses. In the present study, mice orally immunized with a Salmonella vector engineered to stably express ETEC colonization factor antigen I (CFA/I) showed initially elevated serum IgG1 and mucosal IgA anti-CFA/I Ab responses. As expected, mice orally immunized with an E. coli-CFA/I construct elicited poor anti-CFA/I Ab responses. In fact, the addition of cholera toxin during oral E. coli-CFA/I immunization failed to greatly enhance mucosal IgA Ab responses. Seven days after immunization with the Salmonella-CFA/I construct, cytokine-specific ELISPOT showed induction of predominant Th2-type responses in both mucosal and systemic immune compartments supporting the early IgG1 and IgA anti-CFA/I Abs. By 4 weeks, the Th cell response became Th1 cell dominant from the earlier Th2-type responses, as evidenced by increased mucosal and systemic IFN-γ-producing T cells and a concomitant elevation of serum IgG2a Ab responses. This biphasic response offers an alternative strategy for directing Salmonella vector-induced host immunity along a Th2 cell-dependent pathway, allowing for early promotion of mucosal and systemic Abs.

Original languageEnglish (US)
Pages (from-to)6249-6256
Number of pages8
JournalInfection and Immunity
Volume67
Issue number12
StatePublished - Dec 1999
Externally publishedYes

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Enterotoxigenic Escherichia coli
Salmonella typhimurium
Helper-Inducer T-Lymphocytes
Antibody Formation
Immunity
Salmonella
Immunization
Gastrointestinal Tract
Lymphoid Tissue
Immunoglobulin A
Immunoglobulins
Immunoglobulin G
Serum
Escherichia coli
Enzyme-Linked Immunospot Assay
Antigens
Th2 Cells
Th1 Cells
Cholera Toxin
colonization factor antigens

ASJC Scopus subject areas

  • Immunology

Cite this

Pascual, D. W., Hone, D. M., Hall, S., Van Ginkel, F. W., Yamamoto, M., Walters, N., ... Mcghee, J. R. (1999). Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response. Infection and Immunity, 67(12), 6249-6256.

Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response. / Pascual, David W.; Hone, David M.; Hall, Stacy; Van Ginkel, Frederik W.; Yamamoto, Masafumi; Walters, Nancy; Fujihashi, Kohataro; Powell, Robert J.; Wu, Shaoguang; Vancott, John L.; Kiyono, Hiroshi; Mcghee, Jerry R.

In: Infection and Immunity, Vol. 67, No. 12, 12.1999, p. 6249-6256.

Research output: Contribution to journalArticle

Pascual, DW, Hone, DM, Hall, S, Van Ginkel, FW, Yamamoto, M, Walters, N, Fujihashi, K, Powell, RJ, Wu, S, Vancott, JL, Kiyono, H & Mcghee, JR 1999, 'Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response', Infection and Immunity, vol. 67, no. 12, pp. 6249-6256.
Pascual, David W. ; Hone, David M. ; Hall, Stacy ; Van Ginkel, Frederik W. ; Yamamoto, Masafumi ; Walters, Nancy ; Fujihashi, Kohataro ; Powell, Robert J. ; Wu, Shaoguang ; Vancott, John L. ; Kiyono, Hiroshi ; Mcghee, Jerry R. / Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response. In: Infection and Immunity. 1999 ; Vol. 67, No. 12. pp. 6249-6256.
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abstract = "Protective immunity to enterotoxigenic Escherichia coli (ETEC) is antibody (Ab) dependent; however, oral immunization with purified ETEC fimbriae fails to elicit protective immunity as a consequence of antigenic alteration by the gastrointestinal (GI) tract. Unless unaltered ETEC fimbriae can reach the inductive lymphoid tissues of the GI tract, immunity to ETEC cannot be induced. To produce immunity, live vectors, such as Salmonella typhimurium, can effectively target passenger antigens to the inductive lymphoid tissues of the GI tract. By convention, oral immunizations with Salmonella vectors induce CD4+ T helper (Th) cell responses by gamma interferon (IFN-γ)-dominated pathways both to the vector and passenger antigen, resulting in serum immunoglobulin G2a (IgG2a) and modest mucosal IgA Ab responses. In the present study, mice orally immunized with a Salmonella vector engineered to stably express ETEC colonization factor antigen I (CFA/I) showed initially elevated serum IgG1 and mucosal IgA anti-CFA/I Ab responses. As expected, mice orally immunized with an E. coli-CFA/I construct elicited poor anti-CFA/I Ab responses. In fact, the addition of cholera toxin during oral E. coli-CFA/I immunization failed to greatly enhance mucosal IgA Ab responses. Seven days after immunization with the Salmonella-CFA/I construct, cytokine-specific ELISPOT showed induction of predominant Th2-type responses in both mucosal and systemic immune compartments supporting the early IgG1 and IgA anti-CFA/I Abs. By 4 weeks, the Th cell response became Th1 cell dominant from the earlier Th2-type responses, as evidenced by increased mucosal and systemic IFN-γ-producing T cells and a concomitant elevation of serum IgG2a Ab responses. This biphasic response offers an alternative strategy for directing Salmonella vector-induced host immunity along a Th2 cell-dependent pathway, allowing for early promotion of mucosal and systemic Abs.",
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AU - Van Ginkel, Frederik W.

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AU - Walters, Nancy

AU - Fujihashi, Kohataro

AU - Powell, Robert J.

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AU - Vancott, John L.

AU - Kiyono, Hiroshi

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