Border patrols and secret passageways across the intestinal epithelium: response

We are grateful to Drs Isberg and Barnes for their insightful comments on our work1xExtraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Vazquez-Torres, A. et al. Nature. 1999; 401: 804–808Crossref | PubMed | Scopus (371)See all References1. We would like to emphasize that CD18-expressing phagocytes represent not only a gateway for the dissemination of enteric pathogens to distant host sites, but also a mechanism for the elicitation of specific systemic immune responses to antigens encountered at mucosal surfaces. Despite their inability to enter M cells efficiently2xSalmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer’s patches. Jones, B.D. et al. J. Exp. Med. 1994; 180: 15–23Crossref | PubMed | Scopus (541)See all References, 3xNon-invasive Salmonella typhimurium mutants are avirulent because of an inability to enter and destroy M cells of ileal Peyer’s patches. Penheiter, K.L. et al. Mol. Microbiol. 1997; 24: 697–709Crossref | PubMedSee all References, 4xInoculum composition and Salmonella pathogenicity island 1 regulate M-cell invasion and epithelial destruction by Salmonella typhimurium. Clark, M.A. et al. Infect. Immun. 1998; 66: 724–731PubMedSee all References, damage enterocytes5xDistribution of the invA,-B,-C and-D genes of Salmonella typhimurium among other Salmonella serovars: invA mutants of Salmonella typhi are deficient for entry into mammalian cells. Galan, J.E. and Curtiss, R. Jr. Infect. Immun. 1991; 59: 2901–2908PubMedSee all References, 6xEvaluation of Salmonella typhimurium mutants in a model of experimental gastroenteritis. Everest, P. et al. Infect. Immun. 1999; 67: 2815–2821PubMedSee all References, disrupt tight junctions7xSalmonella typhimurium attachment to human intestinal epithelial monolayers (transcellular signalling to subepithelial neutrophils) . McCormick, B.A. et al. J. Cell. Biol. 1993; 123: 895–907Crossref | PubMed | Scopus (294)See all References, 8xTrans-epithelial signaling to neutrophils by salmonellae (a novel virulence mechanism for gastroenteritis) . McCormick, B.A. et al. Infect. Immun. 1995; 63: 2302–2309PubMedSee all References, localize in Peyer’s patches9xSynergistic effect of mutations in invA and lpfC on the ability of Salmonella typhimurium to cause murine typhoid. Baumler, A.J. et al. Infect. Immun. 1997; 65: 2254–2259PubMedSee all References9 or elicit mucosal immunoglobulin (Ig)A immune responses1xExtraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Vazquez-Torres, A. et al. Nature. 1999; 401: 804–808Crossref | PubMed | Scopus (371)See all References1, invasion-deficient Salmonella reach systemic lymphoid organs and trigger a specific IgG humoral immune response. M cells and CD18- expressing phagocytes provide an anatomical basis for the compartmentalization of the immune system, as well as independent cellular routes by which pathogens can enter the host. Many questions remain with regard to the specific site of initial microorganism–phagocyte contact, the functional and phenotypic characteristics of the CD18-expressing cells, and the types of antigen that can be taken up by these cells. We hope that future research will shed light on these important questions and facilitate the exploitation of this pathway for the development of novel vaccine strategies.