Mucosal Immunologic Responses in Cholera Patients in Bangladesh

Author:

Uddin Taher1,Harris Jason B.23,Bhuiyan Taufiqur Rahman1,Shirin Tahmina1,Uddin Muhammad Ikhtear1,Khan Ashraful Islam1,Chowdhury Fahima1,LaRocque Regina C.24,Alam Nur Haque1,Ryan Edward T.245,Calderwood Stephen B.246,Qadri Firdausi1

Affiliation:

1. International Centre for Diarrhoeal Disease Research, Bangladesh, Centre for Health and Population Research, Dhaka, Bangladesh

2. Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

3. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts

4. Department of Medicine, Harvard Medical School, Boston, Massachusetts

5. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts

6. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts

Abstract

ABSTRACT Vibrio cholerae O1 causes dehydrating diarrhea with a high mortality rate if untreated. The infection also elicits long-term protective immunity. Since V. cholerae is noninvasive, mucosal immunity is likely important for protection. In this study, we compared humoral immune responses in the duodenal mucosa and blood of cholera patients at different time points after the onset of disease and compared them with those of healthy controls (HCs). Immune responses to lipopolysaccharide (LPS) and the recombinant cholera toxin B subunit (rCTB) were assessed by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay. Significant increases in V. cholerae LPS-specific IgA and IgG antibody levels were seen in duodenal extracts on day 30, but the levels decreased to baseline by day 180; plasma V. cholerae LPS-specific IgA levels remained elevated longer. Levels of mucosal CTB antibodies also peaked on day 30, but the increase reached statistical significance only for IgG. A significant correlation was found between the CTB antibody-secreting cell (ASC) response in the circulatory system on day 7 and subsequent CTB-specific IgA levels in duodenal extracts on day 30 and the numbers of CTB-specific IgA ASCs in duodenal tissues on day 180. The proportion (0.07%) of mucosal V. cholerae LPS IgA ASCs peaked on day 30 and remained elevated through day 180 compared to that of HCs ( P = 0.03). These results suggest that protective immunity against V. cholerae is not likely mediated by the constitutive secretion of antibodies at the mucosal surface; our results are consistent with those of other studies that suggest instead that anamnestic immune responses of mucosal lymphocytes may play a major role in protection against cholera.

Publisher

American Society for Microbiology

Subject

Microbiology (medical),Clinical Biochemistry,Immunology,Immunology and Allergy

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