Enhanced immunoglobulin A response and protection against Salmonella enterica serovar typhimurium in the absence of the substance P receptor.
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.
Walters
Nancy
N
Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717-3610, USA. dpascual@montana.edu
Trunkle
Theresa
T
Sura
Michael
M
Pascual
David W
DW
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D036781:Fimbriae Proteins / Q000276:immunology; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood*; D016753:Interleukin-10 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D012486:Salmonella typhimurium / Q000276:immunology*
D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D015848:Interleukin-5; D015850:Interleukin-6; D018040:Receptors, Neurokinin-1; C022924:colonization factor antigens; D016753:Interleukin-10; D036781:Fimbriae Proteins