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Infection and Immunity, January 2005, p. 317-324, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.317-324.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Enhanced Immunoglobulin A Response and Protection against Salmonella enterica Serovar Typhimurium in the Absence of the Substance P Receptor

Veterinary Molecular Biology, Montana State University, Bozeman, Montana

Received 20 July 2004/ Returned for modification 11 September 2004/ Accepted 17 September 2004

The development of the neurokinin-1 receptor-deficient (NK1R^–/–) mouse permitted inquiry into the regulation of secretory immunoglobulin A (S-IgA) responses by substance P (SP) after oral immunization with a Salmonella enterica serovar Typhimurium vector expressing colonization factor antigen I (CFA/I) from enterotoxigenic Escherichia coli. In NK1R^–/– mice, mucosal and serum IgA anti-CFA/I fimbrial responses were augmented, while secreted IgG anti-CFA/I fimbrial responses remained unaffected compared to those of BALB/c (NK1R^+/+) mice. Supportive antibody-forming cells were present in the small intestinal lamina propria and spleen. To gain insight as to why the augmented S-IgA responses occurred, minimally, the responses were not attributed to differences in vaccine colonization of Peyer's patch (PP) and spleen or in their respective tissue weights. However, these S-IgA responses were supported by increased numbers of PP CD4⁺ T helper (Th) cells secreting interleukin-5 (IL-5) and IL-6 and splenic CD4⁺ Th cells secreting IL-6 compared to NK1R^+/+ mice. Challenge of naive NK1R^–/– mice with wild-type Salmonella showed improved median survival compared to naive NK1R^+/+ mice. Data from peritoneal macrophage infection studies suggest that this survival is in part contributed by increased IL-10 production. Oral vaccination with Salmonella CFA/I or Salmonella vector showed no significant differences in conferred protection against wild-type challenge for either NK1R^–/– or NK1R^+/+ mice. Thus, these studies suggest that SP mediation contributes to proinflammatory responses to Salmonella infections.

Editor: J. T. Barbieri

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