title: Circulating Gut-Homing (α4β7+) Plasmablast Responses against Shigella Surface Protein Antigens among Hospitalized Patients with Diarrhea.
abstract: Developing countries are burdened with Shigella diarrhea. Understanding mucosal immune responses associated with natural Shigella infection is important to identify potential correlates of protection and, as such, to design effective vaccines. We performed a comparative analysis of circulating mucosal plasmablasts producing specific antibodies against highly conserved invasive plasmid antigens (IpaC, IpaD20, and IpaD120) and two recently identified surface protein antigens, pan-Shigella surface protein antigen 1 (PSSP1) and PSSP2, common to all virulent Shigella strains. We examined blood and stool specimens from 37 diarrheal patients admitted to the Infectious Diseases & Beliaghata General Hospital, Kolkata, India. The etiological agent of diarrhea was investigated in stool specimens by microbiological methods and real-time PCR. Gut-homing (α4β7 (+)) antibody-secreting cells (ASCs) were isolated from patient blood by means of combined magnetic cell sorting and two-color enzyme-linked immunosorbent spot (ELISPOT) assay. Overall, 57% (21 of 37) and 65% (24 of 37) of the patients were positive for Shigella infection by microbiological and real-time PCR assays, respectively. The frequency of α4β7 (+) IgG ASC responders against Ipas was higher than that observed against PSSP1 or PSSP2, regardless of the Shigella serotype isolated from these patients. Thus, α4β7 (+) ASC responses to Ipas may be considered an indirect marker of Shigella infection. The apparent weakness of ASC responses to PSSP1 is consistent with the lack of cross-protection induced by natural Shigella infection. The finding that ASC responses to IpaD develop in patients with recent-onset shigellosis indicates that such responses may not be protective or may wane too rapidly and/or be of insufficient magnitude.
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Sinha
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Ayan
authors.initials: A
authors.lastname: Dey
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Giulietta
authors.initials: G
authors.lastname: Saletti
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Pradip
authors.initials: P
authors.lastname: Samanta
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Partha Sarathi
authors.initials: PS
authors.lastname: Chakraborty
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: M K
authors.initials: MK
authors.lastname: Bhattacharya
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Santanu
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: T
authors.initials: T
authors.lastname: Ramamurthy
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Jae-Ouk
authors.initials: JO
authors.lastname: Kim
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Yang
authors.affiliation: International Vaccine Institute, Seoul, South Korea College of Pharmacy, Hanyang University, Ansan, South Korea.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: International Vaccine Institute, Seoul, South Korea IPMC Nice-Sophia Antipolis, Nice, France czerkinsky@ipmc.cnrs.fr nandyrk.niced@gov.in.
authors.forename: Cecil
authors.initials: C
authors.lastname: Czerkinsky
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India czerkinsky@ipmc.cnrs.fr nandyrk.niced@gov.in.
authors.forename: Ranjan K
authors.initials: RK
authors.lastname: Nandy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000276:immunology*; D000921:Antibody-Producing Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D003967:Diarrhea / Q000473:pathology*; D004405:Dysentery, Bacillary / Q000473:pathology*; D005260:Female; D006760:Hospitalization; D006801:Humans; D016130:Immunophenotyping; D007194:India; D016023:Integrins / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D010950:Plasma Cells / Q000737:chemistry / Q000276:immunology*; D012760:Shigella / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D016023:Integrins; D008565:Membrane Proteins