Circulating Mucosal Associated Invariant T Cells Are Activated in Vibrio cholerae O1 Infection and Associated with Lipopolysaccharide Antibody Responses

Leung, Daniel T.; Bhuiyan, Taufiqur Rahman; Nishat, Naoshin Sharmin; Hoq, Mohammad Rubel; Aktar, Amena; Rahman, Mustafizur; Uddin, Taher; Khan, Ashraful Islam; Chowdhury, Fahima; Charles, Richelle C.; Harris, Jason B.; Calderwood, Stephen B.; Qadri, Firdausi; Ryan, Edward T.

doi:10.1371/journal.pntd.0003076

Cited by 82 publications

(88 citation statements)

References 42 publications

(60 reference statements)

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“…CT and LPS may activate mucosal innate immune responses (49), and abnormalities in innate immune factors have been repetitively associated with susceptibility to cholera (50)(51)(52). We have also recently shown that mucosal invariant intestinal T (MAIT) cells are activated during cholera and that this response correlates with the development of antibodies against T cell-independent LPS but not T cell-dependent CtxB (53). Interestingly, we found a negative association of increasing age and presence of OSP-specific IgA memory B cell responses on day 30, with the youngest children having the most prominent OSP-specific memory B cell IgA responses in peripheral blood as a percentage of total IgA cells.…”

Section: Discussionmentioning

confidence: 99%

O-Specific Polysaccharide-Specific Memory B Cell Responses in Young Children, Older Children, and Adults Infected with Vibrio cholerae O1 Ogawa in Bangladesh

Aktar

Rahman

Afrin

et al. 2016

Clin Vaccine Immunol

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h Cholera caused by Vibrio cholerae O1 confers at least 3 to 10 years of protection against subsequent disease regardless of age, despite a relatively rapid fall in antibody levels in peripheral blood, suggesting that memory B cell responses may play an important role in protection. The V. cholerae O1-specific polysaccharide (OSP) component of lipopolysaccharide (LPS) is responsible for serogroup specificity, and it is unclear if young children are capable of developing memory B cell responses against OSP, a T cell-independent antigen, following cholera. To address this, we assessed OSP-specific memory B cell responses in young children (2 to 5 years, n ‫؍‬ 11), older children (6 to 17 years, n ‫؍‬ 21), and adults (18 to 55 years, n ‫؍‬ 28) with cholera caused by V. cholerae O1 in Dhaka, Bangladesh. We also assessed memory B cell responses against LPS and vibriocidal responses, and plasma antibody responses against OSP, LPS, and cholera toxin B subunit (CtxB; a T cell-dependent antigen) on days 2 and 7, as well as days 30, 90, and 180 after convalescence. In all age cohorts, vibriocidal responses and plasma OSP, LPS, and CtxB-specific responses peaked on day 7 and fell toward baseline over the follow-up period. In comparison, we were able to detect OSP memory B cell responses in all age cohorts of patients with detectable responses over baseline for 90 to 180 days. Our results suggest that OSP-specific memory B cell responses can occur following cholera, even in the youngest children, and may explain in part the age-independent induction of long-term immunity following naturally acquired disease. C holera is a severe diarrheal disease that is endemic in 50 countries and associated with recurrent outbreaks and epidemics, especially in resource-limited settings (1). Vibrio cholerae can be classified into approximately 200 serogroups, and epidemic cholera can be caused by V. cholerae O1 and O139 serogroups (1, 2). V. cholerae O1 organisms can be biochemically typed into classical and El Tor biotypes. The O1 serogroup consists of Ogawa and Inaba serotypes, depending, respectively, on the presence or absence of a 2-O-methyl group in the nonreducing (upstream) terminal sugar of the O-specific polysaccharide (OSP) component of the lipopolysaccharide (LPS) (3, 4). Protection against cholera is serogroup specific, with serogroup specificity being determined by the OSP component of LPS (5-10). Previous infection with V. cholerae O1 provides no protection against cholera caused by V. cholerae O139 and vice versa (9,11,12). Ogawa and Inaba serotypes frequently fluctuate during cholera outbreaks, switching most commonly from Ogawa to Inaba (13). Immune responses against Inaba and Ogawa OSP cross-react, with higher immune responses targeting the homologous infecting serotype. Currently, a hybrid strain of V. cholerae O1 El Tor expressing classical cholera toxin (CT) predominates globally (14,15).Children under 5 years of age in regions where cholera is endemic have the highest burden of disease (16,17), although both children...

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Section: Discussionmentioning

confidence: 99%

O-Specific Polysaccharide-Specific Memory B Cell Responses in Young Children, Older Children, and Adults Infected with Vibrio cholerae O1 Ogawa in Bangladesh

Aktar

Rahman

Afrin

et al. 2016

Clin Vaccine Immunol

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“…The recombinant cholera toxin B subunit (rCTB)-specific IgA and IgG antibodies of patients infected with ETEC and V. cholerae were measured in plasma using a standardized enzyme-linked immunosorbent assay (ELISA) technique, as previously described (16,20). As labile toxin B (LTB) has 80% nucleotide sequence homology and cross-reacts immunologically to CTB (21,22), the plasma responses in the ETEC-infected patients were assessed using CTB as the antigen.…”

Section: Methodsmentioning

confidence: 99%

Enumeration of Gut-Homing β7-Positive, Pathogen-Specific Antibody-Secreting Cells in Whole Blood from Enterotoxigenic Escherichia coli- and Vibrio cholerae-Infected Patients, Determined Using an Enzyme-Linked Immunosorbent Spot Assay Technique

Bhuiyan

Hoq

Nishat

et al. 2016

Clin Vaccine Immunol

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Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) are noninvasive mucosal pathogens that cause acute watery diarrhea in people in developing countries. Direct assessment of the mucosal immune responses to these pathogens is problematic. Surrogate markers of local mucosal responses in blood are increasingly being studied to determine the mucosal immune responses after infection. However, the volume of blood available in children and infants has limited this approach. We assessed whether an approach that first isolates ␤7-positive cells from a small volume of blood would allow measurement of the antigenspecific immune responses in patients with cholera and ETEC infection. ␤7 is a cell surface marker associated with mucosal homing. We isolated ␤7-expressing cells from blood on days 2, 7, and 30 and used an enzyme-linked immunosorbent spot (ELISPOT) assay to assess the gut-homing antibody-secreting cells (ASCs) specific to pathogen antigens. Patients with ETEC diarrhea showed a significant increase in toxin-specific gut-homing ASCs at day 7 compared to the levels at days 2 and 30 after onset of illness and to the levels in healthy controls. Similar elevations of responses to the ETEC colonization factors (CFs) CS6 and CFA/I were observed in patients infected with CS6-and CFA/I-positive ETEC strains. Antigen-specific gut-homing ASCs to the B subunit of cholera toxin and cholera-specific lipopolysaccharides (LPS) were also observed on day 7 after the onset of cholera using this approach. This study demonstrates that a simple ELISPOT assay can be used to study the mucosal immunity to specific antigens using a cell-sorting protocol to isolate mucosal homing cells, facilitating measurement of mucosal responses in children following infection or vaccination. Enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae O1 are two major bacterial causes of severe acute watery diarrhea in developing countries (1). The two pathogens are noninvasive mucosa-associated organisms that colonize the small intestine, resulting in losses of fluid and electrolytes due to the action of enterotoxins. Acute infectious diarrhea is the second most common cause of death in children living in developing countries, surpassed only by acute respiratory diseases, and accounts for approximately 20% of all childhood deaths (2). Cholera toxin (CT) and lipopolysaccharides (LPS) are wellcharacterized antigens and virulence factors of V. cholerae O1. For ETEC, the heat-labile (LT) and heat-stable (ST) enterotoxins, as well as colonization factors (CFs), are important virulence factors (3-5). The CFA/I antigen has been recognized as an important colonization factor of ETEC and has frequently been detected in ETEC isolated from patients with diarrhea. The colonization factor CS6 has been shown to promote binding of ETEC to rabbit and human enterocytes and has frequently been present on ETEC isolated from humans with diarrhea (6, 7).During natural infection and after vaccination, protection from noninvasive pathogens results from induction of a ...

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“…These response patterns and functions contribute to their involvement and protective role against bacterial infections in animal models as well as humans (9,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). In addition, high expression of receptors for IL-18 and IL-12 (9,31,32) provides MAIT cells with the capacity to respond to antigen-presenting cell (APC)-derived cytokines, recently shown to be important for TCR-mediated activation (33,34), as well as to MR1-independent innate responses (35,36).…”

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confidence: 99%

Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines

Dias

Leeansyah

Sandberg

2017

Proc. Natl. Acad. Sci. U.S.A.

182

244

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Mucosa-associated invariant T (MAIT) cells are a large innate-like T-cell subset in humans defined by invariant TCR Vα7.2 use and expression of CD161. MAIT cells recognize microbial riboflavin metabolites of bacterial or fungal origin presented by the monomorphic MR1 molecule. The extraordinary level of evolutionary conservation of MR1 and the limited known diversity of riboflavin metabolite antigens have suggested that MAIT cells are relatively homogeneous and uniform in responses against diverse microbes carrying the riboflavin biosynthesis pathway. The ability of MAIT cells to exhibit microbe-specific functional specialization has not been thoroughly investigated. Here, we found that MAIT cell responses against Escherichia coli and Candida albicans displayed microbe-specific polyfunctional response profiles, antigen sensitivity, and response magnitudes. MAIT cell effector responses against E. coli and C. albicans displayed differential MR1 dependency and TCR β-chain bias, consistent with possible divergent antigen subspecificities between these bacterial and fungal organisms. Finally, although the MAIT cell immunoproteome was overall relatively homogenous and consistent with an effector memory-like profile, it still revealed diversity in a set of natural killer cell-associated receptors. Among these, CD56, CD84, and CD94 defined a subset with higher expression of the transcription factors promyelocytic leukemia zinc finger (PLZF), eomesodermin, and T-bet and enhanced capacity to respond to IL-12 and IL-18 stimulation. Thus, the conserved and innate-like MAIT cells harbor multiple layers of functional heterogeneity as they respond to bacterial or fungal organisms or innate cytokines and adapt their antimicrobial response patterns in a stimulus-specific manner.

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Circulating Mucosal Associated Invariant T Cells Are Activated in Vibrio cholerae O1 Infection and Associated with Lipopolysaccharide Antibody Responses

Cited by 82 publications

References 42 publications

O-Specific Polysaccharide-Specific Memory B Cell Responses in Young Children, Older Children, and Adults Infected with Vibrio cholerae O1 Ogawa in Bangladesh

O-Specific Polysaccharide-Specific Memory B Cell Responses in Young Children, Older Children, and Adults Infected with Vibrio cholerae O1 Ogawa in Bangladesh

Enumeration of Gut-Homing β7-Positive, Pathogen-Specific Antibody-Secreting Cells in Whole Blood from Enterotoxigenic Escherichia coli- and Vibrio cholerae-Infected Patients, Determined Using an Enzyme-Linked Immunosorbent Spot Assay Technique

Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines

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