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Article: MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth.

Cheng, Olivia J / Lebish, Eric J / Jensen, Owen / Jacenik, Damian / Trivedi, Shubhanshi / Cacioppo, Jackson / Aubé, Jeffrey / Beswick, Ellen J / Leung, Daniel T

bioRxiv : the preprint server for biology

2024

Abstract: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions and have ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions and have potentials for use as adoptive cell therapy. However, studies into their anti-cancer activity, including their role in colon cancer, are limited. Using an animal model of colon cancer, we show that peritumoral injection of
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.16.575894
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Article: Syndromic Panel Testing Among Patients With Infectious Diarrhea: The Challenge of Interpreting

Pender, Melissa / Throneberry, S Kyle / Grisel, Nancy / Leung, Daniel T / Lopansri, Bert K

Open forum infectious diseases

2023 Volume 10, Issue 5, Page(s) ofad184

Abstract: Background: Including : Methods: We conducted a retrospective study to determine the frequency at which clinicians characterize PTP and disease severity in adult patients who test positive for CD by GIPCR. We organized subjects into cohorts based on ... ...

Abstract	Background: Including Methods: We conducted a retrospective study to determine the frequency at which clinicians characterize PTP and disease severity in adult patients who test positive for CD by GIPCR. We organized subjects into cohorts based on the status of their CD PCR, glutamate dehydrogenase enzyme immunoassay (GDH), and toxin A/B detection, as well as by high, moderate, or low CD PTP. We used multivariable regression models to describe predictors of toxin positivity. Results: We identified 483 patients with positive CD PCR targets. Only 22% were positive for both GDH and CD toxin. Among patients with a low PTP for CDI, 11% demonstrated a positive CD toxin result compared to 63% of patients with a high PTP. A low clinician PTP for CD infection (CDI) correlated with a negative CD toxin result compared to cases of moderate-to-high PTP for CDI (odds ratio, 0.19 [95% confidence interval, .10-.36]). Up to 64% of patients with negative GDH and CD toxin received CD treatment. Only receipt of prior antibiotics, fever, and a moderate-to-high clinician PTP were statistically significant predictors of toxin positivity. Conclusions: Patients with a positive CD PCR were likely to receive treatment regardless of PTP or CD toxin results. We recommend that CD positivity on GIPCR be interpreted with caution, particularly in the setting of a low PTP.
Language	English
Publishing date	2023-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad184
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Article ; Online: Enhancing Mucosal-Associated Invariant T Cell Function and Expansion with Human Selective Serum.

Labuz, Daniel / Cacioppo, Jackson / Li, Kelin / Aubé, Jeffrey / Leung, Daniel T

ImmunoHorizons

2023 Volume 7, Issue 1, Page(s) 116–124

Abstract: Mucosal-associated invariant T (MAIT) cells are promising innate-like lymphocytes with potential for use in anti-tumor immunotherapy. Existing MAIT cell expansion protocols are associated with potentially decremental phenotypic changes, including ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells are promising innate-like lymphocytes with potential for use in anti-tumor immunotherapy. Existing MAIT cell expansion protocols are associated with potentially decremental phenotypic changes, including increased frequency of CD4+ MAIT cells and higher inhibitory receptor expression. In this study, we compared the effect on expansion of human MAIT cells of a serum replacement, Physiologix XF SR (Phx), with traditional serum FBS for supplementing RPMI 1640 media. Using flow cytometry, we found that Phx supported a significantly higher proliferative capacity for MAIT cells and resulted in a lower frequency of CD4+ MAIT cells, which have been associated with reduced Th1 effector and cytolytic functions. We saw that culturing MAIT cells in Phx led to better survival of MAIT cells and lower frequency of PD-1+ MAIT cells than FBS-supplemented media. Functionally, we saw that Phx supplementation was associated with a higher frequency of IFN-γ+ MAIT cells after stimulation with Escherichia coli than FBS-supplemented RPMI. In conclusion, we show that MAIT cells cultured in Phx have higher proliferative capacity, lower expression of inhibitory receptors, and higher capacity to produce IFN-γ after E. coli stimulation than FBS-supplemented RPMI. This work shows that expanding MAIT cells with Phx compared with FBS-supplemented RPMI results in a more functionally desirable MAIT cell for future anti-tumor immunotherapy.
MeSH term(s)	Humans ; Mucosal-Associated Invariant T Cells/metabolism ; Escherichia coli ; Interferon-gamma/metabolism ; Flow Cytometry
Chemical Substances	Interferon-gamma (82115-62-6)
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2573-7732
ISSN (online)	2573-7732
DOI	10.4049/immunohorizons.2200082
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Article ; Online: A subset of follicular helper-like MAIT cells can provide B cell help and support antibody production in the mucosa.

Jensen, Owen / Trivedi, Shubhanshi / Meier, Jeremy D / Fairfax, Keke C / Hale, J Scott / Leung, Daniel T

Science immunology

2022 Volume 7, Issue 67, Page(s) eabe8931

Abstract: Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that aid in protection against bacterial pathogens at mucosal surfaces through the release of inflammatory cytokines and cytotoxic molecules. Recent evidence suggests that MAIT ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that aid in protection against bacterial pathogens at mucosal surfaces through the release of inflammatory cytokines and cytotoxic molecules. Recent evidence suggests that MAIT cells can also provide B cell help. In this study, we describe a population of CXCR5
MeSH term(s)	Adolescent ; Adult ; Animals ; Antibodies/immunology ; Antibody Formation/immunology ; B-Lymphocytes/immunology ; Child ; Child, Preschool ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mucosal-Associated Invariant T Cells/immunology ; Mucous Membrane/immunology ; Mucous Membrane/microbiology ; Vibrio cholerae/immunology
Chemical Substances	Antibodies
Language	English
Publishing date	2022-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abe8931
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Article: Assessment of Model Estimated and Directly Observed Weather Data for Etiological Prediction of Diarrhea.

Brintz, Ben J / Colston, Josh M / Ahmed, Sharia M / Chao, Dennis L / Zaitschik, Ben / Leung, Daniel T

medRxiv : the preprint server for health sciences

2023

Abstract: Recent advances in clinical prediction for diarrheal etiology in low- and middle-income countries have revealed that addition of weather data improves predictive performance. However, the optimal source of weather data remains unclear. We aim to compare ... ...

Abstract	Recent advances in clinical prediction for diarrheal etiology in low- and middle-income countries have revealed that addition of weather data improves predictive performance. However, the optimal source of weather data remains unclear. We aim to compare model estimated satellite- and ground-based observational data with weather station directly-observed data for diarrheal prediction. We used clinical and etiological data from a large multi-center study of children with diarrhea to compare these methods. We show that the two sources of weather conditions perform similarly in most locations. We conclude that while model estimated data is a viable, scalable tool for public health interventions and disease prediction, directly observed weather station data approximates the modeled data, and given its ease of access, is likely adequate for prediction of diarrheal etiology in children in low- and middle-income countries.
Language	English
Publishing date	2023-10-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.12.23296959
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Article ; Online: Targeted multi-omic analysis of human skin tissue identifies alterations of conventional and unconventional T cells associated with burn injury.

Labuz, Daniel R / Lewis, Giavonni / Fleming, Irma D / Thompson, Callie M / Zhai, Yan / Firpo, Matthew A / Leung, Daniel T

eLife

2023 Volume 12

Abstract: Burn injuries are a leading cause of unintentional injury, associated with a dysfunctional immune response and an increased risk of infections. Despite this, little is known about the role of T cells in human burn injury. In this study, we compared the ... ...

Abstract	Burn injuries are a leading cause of unintentional injury, associated with a dysfunctional immune response and an increased risk of infections. Despite this, little is known about the role of T cells in human burn injury. In this study, we compared the activation and function of conventional T cells and unconventional T cell subsets in skin tissue from acute burn (within 7 days from initial injury), late phase burn (beyond 7 days from initial injury), and non-burn patients. We compared T cell functionality by a combination of flow cytometry and a multi-omic single-cell approach with targeted transcriptomics and protein expression. We found a significantly lower proportion of CD8+ T cells in burn skin compared to non-burn skin, with CD4+ T cells making up the bulk of the T cell population. Both conventional and unconventional burn tissue T cells show significantly higher IFN-γ and TNF-α levels after stimulation than non-burn skin T cells. In sorted T cells, clustering showed that burn tissue had significantly higher expression of homing receptors CCR7, S1PR1, and SELL compared to non-burn skin. In unconventional T cells, including mucosal-associated invariant T (MAIT) and γδ T cells, we see significantly higher expression of cytotoxic molecules GZMB, PRF1, and GZMK. Multi-omics analysis of conventional T cells suggests a shift from tissue-resident T cells in non-burn tissue to a circulating T cell phenotype in burn tissue. In conclusion, by examining skin tissue from burn patients, our results suggest that T cells in burn tissue have a pro-inflammatory rather than a homeostatic tissue-resident phenotype, and that unconventional T cells have a higher cytotoxic capacity. Our findings have the potential to inform the development of novel treatment strategies for burns.
MeSH term(s)	Humans ; Multiomics ; T-Lymphocyte Subsets ; Skin/metabolism ; CD8-Positive T-Lymphocytes ; Burns/metabolism
Language	English
Publishing date	2023-02-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.82626
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Article ; Online: Sex difference in the discordance between Abbott Architect and EuroImmun serological assays.

Hartsell, Joel D / Leung, Daniel T / Zhang, Yue / Delgado, Julio C / Alder, Stephen C / Samore, Matthew H

PeerJ

2023 Volume 11, Page(s) e15247

Abstract: Background: This study evaluated the discordance between Abbott Architect SARS-CoV-2 IgG and EUROIMMUN SARS-COV-2 ELISA in a seroprevalence study.: Methods: From June 10 to August 15, 2020, 8,246 specimens were dually evaluated by the Abbott ... ...

Abstract	Background: This study evaluated the discordance between Abbott Architect SARS-CoV-2 IgG and EUROIMMUN SARS-COV-2 ELISA in a seroprevalence study. Methods: From June 10 to August 15, 2020, 8,246 specimens were dually evaluated by the Abbott Architect SARS-CoV-2 IgG (Abbott) and the EUROIMMUN SARS-CoV-2 ELISA (EI) assays. Sex-stratified phi correlation coefficients were calculated to evaluate the concordance between Abbott and EI assay's quantitative results. Multivariable mixed-effect logistic models were implemented to evaluate the association between assay positivity and sex on a low prevalence sample while controlling for age, race, ethnicity, diabetes, cardiovascular disease, hypertension, immunosuppressive therapy, and autoimmune disease. Results: EI positivity among males was 2.1-fold that of females; however, no significant differences in Abbott positivity were observed between sexes. At the manufacturer-recommended threshold, the phi correlation coefficient for the Abbott and EI qualitative results among females (Φ = 0.47) was 34% greater than males (Φ = 0.35). The unadjusted and fully adjusted models yielded a strong association between sex and positive EI result for the low prevalence subgroup (unadjusted OR: 2.24, CI: 1.63, 3.11, adjusted OR: 3.40, CI: 2.15, 5.39). A similar analysis of Abbott positivity in the low prevalence subgroup did not find an association with any of the covariates examined. Significant quantitative and qualitative discordance was observed between Abbott and EI throughout the seroprevalence study. Our results suggest the presence of sex-associated specificity limitations with the EI assay. As these findings may extend to other anti-S assays utilized for SARS-CoV-2 seroprevalence investigations, further investigation is needed to evaluate the generalizability of these findings.
MeSH term(s)	Female ; Humans ; Male ; SARS-CoV-2 ; COVID-19 ; Sex Characteristics ; Seroepidemiologic Studies ; Sensitivity and Specificity ; Antibodies, Viral ; Immunoglobulin G
Chemical Substances	Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2023-07-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359 ; 2167-8359
ISSN (online)	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.15247
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Article ; Online: Genomic Characterization of 2

Brown, D Garrett / Wahlig, Taylor A / Ma, Angela / Certain, Laura K / Chalmers, Peter N / Fisher, Mark A / Leung, Daniel T

Pathogens & immunity

2023 Volume 8, Issue 1, Page(s) 64–76

Abstract: Background: Cutibacterium acnes: Methods: We used standard microbiological methods for phenotypic characterization and performed whole genome sequencing on 2 : Results: Antibiotic susceptibility testing showed beta-lactamase negative and low ... ...

Abstract	Background: Cutibacterium acnes Methods: We used standard microbiological methods for phenotypic characterization and performed whole genome sequencing on 2 Results: Antibiotic susceptibility testing showed beta-lactamase negative and low minimal inhibitory concentrations to all antibiotics tested, with the exception of metronidazole. We assembled complete genomes of the 2 isolates, which are approximately 2.5 megabases in length. The isolates belong to the single-locus sequence type (SLST) H1 and the multi-locus sequence type (MLST) IB. Both isolates have similar composition of known virulence genes, and we found no evidence of plasmids but did find phage-associated genes. Notably, the 2 genomes are 99.97% identical but contain a large genomic inversion encompassing approximately half of the genome. Conclusions: This is the first characterization of this large-scale genomic inversion in nearly identical isolates from the same wound. This report adds to the limited numbers of publicly available infection-associated complete genomes of
Language	English
Publishing date	2023-10-05
Publishing country	United States
Document type	Journal Article
ISSN	2469-2964
ISSN (online)	2469-2964
DOI	10.20411/pai.v8i1.606
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Article ; Online: Drivers of inappropriate use of antimicrobials in South Asia: A systematic review of qualitative literature.

Murray, Jennifer L / Leung, Daniel T / Hanson, Olivia R / Ahmed, Sharia M / Pavia, Andrew T / Khan, Ashraful I / Szymczak, Julia E / Vaughn, Valerie M / Patel, Payal K / Biswas, Debashish / Watt, Melissa H

PLOS global public health

2024 Volume 4, Issue 4, Page(s) e0002507

Abstract: Antimicrobial resistance is a global public health crisis. Effective antimicrobial stewardship requires an understanding of the factors and context that contribute to inappropriate use of antimicrobials. The goal of this qualitative systematic review was ...

Abstract	Antimicrobial resistance is a global public health crisis. Effective antimicrobial stewardship requires an understanding of the factors and context that contribute to inappropriate use of antimicrobials. The goal of this qualitative systematic review was to synthesize themes across levels of the social ecological framework that drive inappropriate use of antimicrobials in South Asia. In September 2023, we conducted a systematic search using the electronic databases PubMed and Embase. Search terms, identified a priori, were related to research methods, topic, and geographic location. We identified 165 articles from the initial search and 8 upon reference review (n = 173); after removing duplicates and preprints (n = 12) and excluding those that did not meet eligibility criteria (n = 115), 46 articles were included in the review. We assessed methodological quality using the qualitative Critical Appraisal Skills Program checklist. The studies represented 6 countries in South Asia, and included data from patients, health care providers, community members, and policy makers. For each manuscript, we wrote a summary memo to extract the factors that impede antimicrobial stewardship. We coded memos using NVivo software; codes were organized by levels of the social ecological framework. Barriers were identified at multiple levels including the patient (self-treatment with antimicrobials; perceived value of antimicrobials), the provider (antimicrobials as a universal therapy; gaps in knowledge and skills; financial or reputational incentives), the clinical setting (lack of resources; poor regulation of the facility), the community (access to formal health care; informal drug vendors; social norms), and policy (absence of a regulatory framework; poor implementation of existing policies). This study is the first to succinctly identify a range of norms, behaviors, and policy contexts driving inappropriate use of antimicrobials in South Asia, emphasizing the importance of working across multiple sectors to design and implement approaches specific to the region.
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0002507
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Article ; Online: A Novel Luminescence-Based Serum Bactericidal Assay for Vibrio cholerae Reduces Assay Variation, Is Time- and Cost-Effective, and Directly Measures Continuous Titer Values.

Wahlig, Taylor A / Brintz, Ben J / Prettyman, Melanie / Azman, Andrew S / Leung, Daniel T

The American journal of tropical medicine and hygiene

2021 Volume 105, Issue 3, Page(s) 622–626

Abstract: Cholera remains a significant public health burden worldwide, and better methods for monitoring cholera incidence would enhance the effectiveness of public health interventions. The serum bactericidal assay (SBA) has been used extensively for Vibrio ... ...

Abstract	Cholera remains a significant public health burden worldwide, and better methods for monitoring cholera incidence would enhance the effectiveness of public health interventions. The serum bactericidal assay (SBA) has been used extensively for Vibrio cholerae vaccine assessments and serosurveillance. Current SBA approaches for V. cholerae rely on colony enumeration or optical density (OD600nm) readings to measure viable bacteria following complement-mediated lysis. These methods provide titer values that are constrained to discrete dilution values and rely on bacterial outgrowth, which is time consuming and prone to variation. Detection of bacterial proteins following complement-mediated lysis presents a faster and potentially less variable alternative approach independent of bacterial outgrowth. Here, we present an SBA that measures luciferase luminescence driven by lysis-released adenylate kinase. This approach is faster and less variable than growth-dependent SBAs and directly measures continuous titer values. This novel SBA method can potentially be applied to other bacteria of interest.
MeSH term(s)	Antibodies, Bacterial/immunology ; Cholera/epidemiology ; Cholera/immunology ; Cholera/prevention & control ; Cholera Vaccines/therapeutic use ; Cost-Benefit Analysis ; Epidemiological Monitoring ; Humans ; Immunogenicity, Vaccine ; Luminescent Measurements ; Reproducibility of Results ; Seroepidemiologic Studies ; Serum Bactericidal Antibody Assay/methods ; Time Factors ; Vibrio cholerae/immunology
Chemical Substances	Antibodies, Bacterial ; Cholera Vaccines
Language	English
Publishing date	2021-07-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.21-0136
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