Enhanced immunoglobulin A response and protection against Salmonella enterica serovar Typhimurium in the absence of the substance P receptor

Abstract

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 interieukin-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.