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Infect. Immun. doi:10.1128/IAI.01856-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mucosal and systemic immune responses in patients with diarrhea due to CS6 expressing enterotoxigenic Escherichia coli

International Centre for Diarrhoeal Disease Research, Bangladesh, GPO Box 128, Dhaka 1000, Bangladesh, Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA, Department of Infectious Diseases, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, UK; Göteborg University Vaccine Research Institute (GUVAX) and Department of Microbiology and Immunology, the Sahlgrenska Academy at Göteborg University, Box 435 S-40530, Göteborg, Sweden

^* To whom correspondence should be addressed. Email: fqadri{at}icddrb.org.

	Abstract

The colonization factor CS6 expressed by enterotoxigenic Escherichia coli (ETEC) is a nonfimbrial polymeric protein. A substantial proportion of ETEC isolated from patients both in endemic settings and in travelers to these regions are caused by ETEC expressing CS6, either as CS6 alone or in combination with the fimbrial colonization factor CS5 or CS4. However, relatively little is known about the natural immune responses elicited against CS6 expressed by ETEC strains causing disease. We have studied patients hospitalized with diarrhea (n=46) with CS6 expressing ETEC (CS6 or CS5+CS6-ETEC) with a disease spectrum ranging from severe (27%) to moderate and mild dehydration (73%). Using recombinant CS6 antigen, we have found that over 90% of the patients responded with mucosal immune responses to CS6 determined as IgA-antibody secreting cells [ASC], or antibody in lymphocyte supernatant [ALS] and about 57% responded with CS6 specific IgA antibodies in feces. Over 80% of the patients showed IgA seroconversion to CS6. Significant increases in anti-CS6 antibodies of IgG isotype were also observed in assays for ASC (75%), ALS (100%) and serum (70%). These studies demonstrate that patients hospitalized with the non-invasive enteric pathogen, CS6-ETEC, respond with both mucosal and systemic antibody against CS6. Studies are needed to determine if the anti-CS6 responses may be protective against reinfection, and if protective levels of CS6 immunity may be induced by vaccination.

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