RESUMO
Oral cholera vaccination is used to induce immune responses in the intestines to protect against cholera infection. However, oral vaccination may also affect immune responses in other mucosal tissues. To study this, tissue-specific homing potential and kinetics of B-cell responses were characterized after oral cholera vaccination. Healthy adult volunteers received two doses of Dukoral® and blood, saliva, nasal wash, and fecal samples were collected over time to detect vaccine-specific antibodies. Additionally, homing potential of lymphocytes to small intestine, colon, airways, skin, and periphery was measured by expression of Integrin ß1 and ß7, CCR9, CCR10, CCR7, and CLA. After vaccination, antibody responses to cholera toxin B (CTB) and Dukoral® were detected in serum and nasal wash. CTB-specific memory B cells in peripheral blood and tissue homing profiles of memory B cells peaked at day 18. IgA+ memory B cells expressed markers that enable homing to the airways and colon, while IgA- memory B cells primarily expressed small-intestine-homing markers. These data show that oral cholera vaccination has a differential effect on immune responses in various mucosal sites, including the respiratory tract.
Assuntos
Linfócitos B/imunologia , Vacinas contra Cólera/imunologia , Cólera/imunologia , Intestino Grosso/imunologia , Sistema Respiratório/imunologia , Linfócitos T/imunologia , Vibrio cholerae/fisiologia , Administração Oral , Adolescente , Adulto , Movimento Celular , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Imunoglobulina A/metabolismo , Memória Imunológica , Intestino Grosso/microbiologia , Ativação Linfocitária , Masculino , Gravidez , Sistema Respiratório/microbiologia , Vacinação , Adulto JovemRESUMO
BACKGROUND: Several probiotic strains have been shown to enhance human resistance to infectious disease. It is speculated that these strains may impose this effect by excretion of anti-microbial components, by competing with pathogens for intestinal nutrients and/or mucosal adhesion sites or modulating the immune system. OBJECTIVE: A parallel, double-blind, placebo-controlled 4-week intervention was performed in healthy males, to study the effect of a blend of probiotic bacteria (Lactobacillus helveticus Rosell-52, Lactobacillus rhamnosus Rosell-11, Bifidobacterium longum ssp. longum Rosell-175) and a probiotic yeast (Saccharomyces cerevisiae var boulardii CNCM I-1079) on enterotoxigenic Escherichia coli (ETEC) challenge. Primary outcomes studied were fecal ETEC excretion and total fecal output per day. SUBJECTS/METHODS: Subjects were randomized to the probiotic (5 × 10(9) colony-forming units (CFUs); twice daily; n=30) or placebo group (twice daily; n=30). After 2 weeks, subjects were orally challenged with a live attenuated ETEC (3 × 10(9) CFU), previously demonstrated to induce mild, short-lived symptoms of a foodborne infection. Before and after ETEC challenge, subjects collected 24 h fecal samples. Compliance to study guidelines, stool consistency (Bristol Stool Score), stool frequency, and frequency and severity of gastrointestinal (GI) complaints were recorded by the subjects on a Daily Record Questionnaire. RESULTS: ETEC challenge induced a significant increase in fecal ETEC excretion in both groups. However, a statistically significant increase in fecal output was only observed in the probiotic group. ETEC challenge resulted in a decrease in the percentage of fecal dry weight, and an increase in reported Bristol Stool Score, stool frequency and GI complaints. Dietary probiotics significantly decreased the percentage of fecal dry weight. In addition, ETEC increased C-reactive protein, total secretory Immunoglobulin A (IgA) and Immunoglobulin G Colonization Factor Antigen II. CONCLUSION: Dietary probiotics did not increase resistance to oral attenuated ETEC challenge in human subjects.